Please Note: Fallout 3 is a very open-ended game. This is just a guide and by no means do you have to follow every little detail or instruction to complete the game. There are many ways to proceed through the game. It's recommended to at least try your "own path" through the game (at least your first time through) for the most enjoyment and if you want to avoid SPOILERS. However, if you do get stuck on a specific quest and become frustrated the walkthrough is always an option. 
After starting a new game, an intro scene commences. Then you witness your character's birth, where you have the first of two opportunities to choose a name, gender, race and customize his or her appearance. The sex you choose can change dialogue options with NPCs, but other than that gender has no significant impact in the game. After you are finished with your appearance you begin your first quest, Baby Steps. 

 Baby Steps
Simply a basic instruction on how to move and interact with the environment. Just follow the instructions, escape from your stall, select your attributes in the S.P.E.C.I.A.L. book (you will get another chance to change those at the end of Escape!). Following your father out of the room will end the "quest". 

 Growing Up Fast

Your father greets you at your 10th birthday party and is shortly interrupted by the Overseer who gives you your Pip-Boy 3000. 
After you have received your Pip-Boy, walk towards Amata and she initiates a conversation with you. She gives you Grognak the Barbarian as a present. Next, talk to Stanley to receive a Pre-War Baseball Cap. Then talk to Old Lady Palmer and she give you a Sweetroll. Once Andy has destroyed your birthday cake, Butch DeLoria demands the sweetroll, leaving you with various choices to deal with the situation. If you get in a fight it is broken up by Officer Gomez and Butch gets in trouble. 
Shortly after, the intercom rings and once your Dad has answered it he lets you know that Jonas has a surprise for you down on the Reactor level. Exiting the room where the party is being held, turn right down the hall, and then make the first left. Signs direct you towards the reactor, where Jonas is waiting. He asks you why you are down there, apparently making a joke. After a brief dialog, Dad comes down and gives you your surprise, a BB Gun with 50 BB's, which you can try out on a couple of stationary targets and a Radroach. After you kill the Radroach your father will tell Jonas to take a picture of you and him, simply stand in front of your dad and the camera flash will throw you into six years later. 

Future Imperfect

 
The quest starts with your Dad talking to you about the G.O.A.T. you will have to take in class today. Head through the door (do not forget to grab the Bobblehead: Medicine on your dad's desk), or wait for Jonas to walk through the door. Head straight out to the Hall and turn right to get to the classroom. 
You will encounter Amata being bothered by the Tunnel Snakes. This your first opportunity to earn either good or bad karma, depending on whether you choose to help Amata, do nothing or make things even worse for her. 
After the encounter, follow the other kids into the classroom and approach Mr. Brotch. If you select certain options in this conversation you can skip the G.O.A.T. entirely and select your skills. Otherwise find a seat and sit down as you are told, answer all the questions and when you are done turn in your test. You get pre-set tag skills based on your results but you can change them to whatever you want by speaking to Mr. Brotch after the test. Leave the classroom when you are done. 

Main quests

Escape!

Sweet childhood, gone so soon... You are woken up by Amata who fills you in on the situation: Your father is gone, her father is crazy, Jonas is dead, all the guards are out there looking for you and the vault is infested with radroaches. Time to grab your stuff and get out of here. According to her, your best chance is to make it to the Overseer's office and use her father's secret tunnel to the vault exit. Also before you leave your room be careful to take supplies from your room, you can be quick to forget that there is a first aid box behind Amata as you wake up, it contains 10 Stimpaks. Also to your left there is the BB Gun and the 50 BBs, plus there is a baseball, a baseball bat, and a catchers mitt. Plus there is a trunk even more to the left containing a Vault 101 Utility Jumpsuit which gives +5 in the "Repair" and "Lockpick" skills. 
Once you are out of your room, head to the left. After a bit you will encounter Butch. Your favourite childhood bully wants you to help his mother who is being attacked by radroaches, and will reward you with a the Tunnel Snake Outfit and good karma. Continue up the stairs, go past Officer Gomez and through the door to the Atrium. 
When you enter the Atrium you witness the not very successful attempt of two vault dwellers to follow your father's footsteps out of the vault. You can kill the guards but the door behind them is locked beyond your lockpicking abilities. Go through the door next to the entrance corridor and up to the second level. Follow the signs to the Overseer's Office. After an encounter with the Security Chief you eventually hear the Overseer interrogating his daughter about your whereabouts. You have to get the Overseer's office key (either from his corpse or his room) in order to be able to enter his office. Once there, log into his computer and open the secret tunnel. 
Follow the tunnel until you reach a door. Use the switch on the right wall in the small room on the other side. Go through the hole in the wall and into the large room, walk past the stairs and use the control pad. Sirens go off and the vault door opens. Amata comes down and says goodbye, promptly followed by a pair of guards trying to kill you. 
Then you are home free to the Capital Wasteland. Upon leaving the vault, you have a last chance to change your stats, skills, gender and appearance before walking into the sunlight for the first time in your life. 

Following in His Footsteps
 
You are prompted to investigate the nearby town of Megaton for information about Dad. Arriving there after a short walk, everybody points you to Moriarty, owner of the local saloon. There are various ways to obtain the information from Moriarty: pay him, steal it from his computer or convince Nova to give you the password, do a quest for him, just to mention a few. Whichever way you choose you finally learn that Dad went to GNR after leaving Megaton. It is recommended to go there well-equipped as you are about to encounter your first super-mutant enemies. 
The easiest way to GNR is through the old Metro tunnels. Head to the first Metro Station you can find (for instance Friendship Heights or Farragut West Metro Station) and follow the quest marker until you arrive at Chevy Chase. Exiting to the surface you will soon encounter Sarah Lyons and her Brotherhood of Steel platoon who are trying to clear out the super-mutants in the vicinity of GNR. Follow the group once it starts its attack and eventually you will arrive at the GNR plaza. Once all the regular super-mutants are dead, the Brotherhood members and you are attacked by a Behemoth. Conveniently, there is a Fatman nearby on the body of a dead BoS fighter by the fountain which makes fighting the Behemoth much easier (provided you do not blow yourself up with it). 
When the beast is dead, you are allowed to enter the GNR building at last. Make your way up to the top floor, enter Three Dog's studio and talk to the DJ. To get him to tell you where your father went from here, you have to convince him either with Speech or by doing the Galaxy News Radio quest for him. Either way he will eventually tell you to talk to Dr. Li in Rivet City. 
Note: This entire quest can be skipped simply by talking to Dr. Li in Rivet City. This will advance the questline to Scientific Pursuits even if Three Dog has not told you about her yet and you never talked to Moriarty or Three Dog. However, this may cause the achievement not to be granted. 
Galaxy News Radio

If you can neither convince Three Dog to tell you about your father's whereabouts by using Speech nor have already talked to Dr. Li in Rivet City prior to talking to the DJ, you will have to do this side quest in order to gain his favour. 
Three Dog wants you to restore GNR's broadcasting capabilities which have been seriously limited ever since a super mutant decided to use his broadcasting dish as target practice. You have to get a new dish from the mutant-infested Museum of Technology and install it on top of the Washington Monument. Once this has been completed, Three Dog is willing to help you find your father (and you will be able to tune in to GNR from the whole Wasteland). You may also speak to Three Dog and undertake this side quest later even if he has already shared what he knows about your father. 
Note: This quest is not part of the main storyline but its completion may be required to be able to advance in the main quest. 

 Scientific Pursuits

Time to talk to Dr. Li in Rivet City. Make your way through the Metro tunnels or simply quick-travel (if you have been there before) and once inside, follow the signs reading "Science Lab" where Madison Li is usually to be found. She provides you with some information on Project Purity and tells you to go look for James at Jefferson Memorial. 
Fortunately, the memorial is just a short walk away. When you arrive there, enter through the metal door labeled "Gift Shop". Jefferson Memorial, like its surrounding area is infested by super-mutants, so be prepared. Several of Dad's holotapes are scattered in the various levels of the memorial which will tell you about the time before your birth and your father's more recent efforts to restart the project. Tape #10 which is found in the Rotunda, Project Purity's control room, indicates that your father has left for Vault 112 already. 
Vault 112 is located underneath Smith Casey's Garage. Activating the control switch inside the Garage allows access to a lower level leading directly to the Vault 112 door. Once you step inside, a Robobrain approaches you, insisting that you don the Vault 112 Jumpsuit it provides you with before asking you to enter a Tranquility Lounger. 
Continuing downstairs, you find a number of pods in a circle. Open the only one that is not either occupied or broken. Sitting down in the pod will end this quest and begin Tranquility Lane. 

Tranquility Lane

Upon entering the pod in Vault 112 at the end of Scientic Pursuits you find yourself in a virtual reality simulation of a pre-war neighbourhood called Tranquility Lane. The residents ask you to go play with Betty (who really is Stanislaus Braun) at the playground in the middle of the area. 
There are two possibilities to finish this quest: you can either fulfil Betty's wishes, collecting a lot of bad karma along the way, or abort the simulation via the Fail-Safe Terminal. 
Playing along with Betty: Betty asks you to complete a series of more and more violent tasks. If you choose to grant her wishes you collect a lot of bad karma along the way and finally Betty will release James (who is Doc, the dog at the playground) and you from the simulation as a reward for providing him with a lot of entertainment. 
The Fail-Safe Terminal: For the good karma alternative, speak to Old Lady Dithers. The other residents warn you that she is supposedly insane which is simply caused by the fact that she is the only resident who is aware that they are all just part of a simulation. She will point you to the Abandoned House which according to her houses the Fail-Safe Terminal. 
Inside the house you find a set of unusual objects which make noises when activated. If you enter the proper sequence (radio, pitcher, gnome, pitcher, concrete block, gnome, cola bottle), the terminal appears and allows you to start the "Chinese Invasion" scenario. This causes a Chinese soldier to appear and kill all the residents (except Braun, your father and you) permanently. Speaking to Braun, he will lament that he is now alone and trapped forever within the simulation. You can then leave Tranquility Lane as Braun cannot stop you any more. 
As soon as the pod opens, James runs up to you and begins a conversation, relaying that he had intended to discuss Project Purity with Braun in an attempt to figure out whether the G.E.C.K. would help making Project Purity succeed but had been duped into entering the simulation. After some dialogue, he says he is returning to Rivet City to meet with Dr. Li and resume the project. You can either join up with him immediately or meet him up with him at Rivet City's Science Lab later. 
Note: Stumbling upon Vault 112 and completing "Tranquility Lane" before its point in the story can cause an error with the "Tranquility Lane" achievement. 

The Waters of Life

When you arrive at Rivet City's Science Lab, James convinces Dr. Li to reactivate Project Purity. After talking to him he asks you to meet him and the scientists there. Upon arrival, your father asks you to clear the project area of enemy presence (if you haven't already done so during your last visit). Once you have done so, escort him and the other scientists to the control room in the Rotunda. 
As soon as your father arrives there, he asks you to perform a couple of routine maintenance tasks. When you are about drain the intake pipes, you witness the arrival of Enclave soldiers in a Vertibird. Fight your way back to the control room and dispatch any power-armored Enclave soldiers in your path to reach your father. 
When you arrive at the Rotunda, Dr. Li is locked out of the main area, while Janice Kaplinski, James, Colonel Autumn and two Enclave soldiers are locked in. You are forced to watch Autumn execute Janice to get James to give up control of the project and help Enclave scientists get it online. James apparently admits defeat and heads over to the controls but instead of obeying Autumn's orders, he uses the controls to flood the area with radiation, sacrificing himself to kill the Enclave soldiers and knock Autumn unconscious. 
You must then escort Dr. Li and the surviving Scientists through the Taft Tunnels to the Citadel. Killing more Enclave soldiers and feral ghouls along the way, you eventually arrive at the end of the tunnel, directly in front of the Citadel. Entering the Brotherhood of Steel stronghold completes the quest. 

Picking up the Trail

?Little Lamplight 
Main article: Picking up the Trail 
Elder Owyn Lyons tells you to talk to Scribe Rothchild who might be able to help you with your search for a G.E.C.K.. Rothchild sends you to an old Vault-Tec terminal in the Citadel's A-Ring where you find out that Vault 87 received such a device. Returning to Rothchild, he has bad news for you: The vault's entrance is irradiated, making passing through completely impossible. However, he hints there might be an alternative way to get into the vault. This way is through the nearby Lamplight Caverns. 
Entering the caverns, you are eventually stopped by Mayor MacCready at the gates of Little Lamplight. You can gain entrance either by passing a Speech check, using the Child at Heart perk or doing the sidequest Rescue from Paradise (see below). 
Once you are allowed to enter Little Lamplight, there are two ways to proceed to Vault 87: 
Survive Murder Pass: You must speak with Mayor MacCready or Princess to have the gate to Murder Pass opened. Kill the Super Mutants along the way and you eventually arrive at the vault entrance. 
Hack the back door: Mayor MacCready tells you that there is a door in the Great Chamber that does not open. This happens to be a back door to Vault 87. You can hack the computer terminal once Joseph has restored its power. 
Both doors lead to the same area in the vault. 

Rescue from Paradise

If you cannot convince Mayor MacCready to let you into Little Lamplight by using either Speech or the Child at Heart perk you will have to rescue Sammy, Squirrel and Penny from the slavers in Paradise Falls in order to gain MacCready's trust und thus access to the town. 
Note: This quest is not part of the main storyline but its completion may be required to be able to advance in the main quest. 

Finding the Garden of Eden

Once inside Vault 87 you find yourself confronted with yet more Super Mutants. The way through the vault is fairly linear, simply keep going (and fighting) until you arrive at the Test Labs. Here you eventually encounter an imprisoned Super Mutant called Fawkes who wants to talk via intercom. If you do so, Fawkes offers to retrieve the Garden of Eden Creation Kit from the irradiated halls above in exchange for freedom. 
The radiation level around the G.E.C.K. storage room is indeed very high (although not Vault-87-entrance-instant-death-high) leaving you with the options to either free Fawkes and have her retrieve the device or maximize your Radiation resistance and try to get it yourself. 
The room with the G.E.C.K. can be found by going left from Fawkes' cell. If you release him, he leads you there and engages the remaining enemies; otherwise, you will have to go there on your own. A locked room just upstairs holds various equipment such as a Radiation Suit which comes in handy when you are trying to retrieve the G.E.C.K. yourself. Once you are in possession of the G.E.C.K., make your way back down to the previously locked door. 
As a reward for your effort, you are now ambushed by a contingent of Enclave soldiers who take you and the G.E.C.K. to Raven Rock, the Enclave's main base in the Capital Wasteland. 

 The American Dream



You wake up in a cell at Raven Rock where Colonel Autumn interrogates you with the goal of finding out the access code to Project Purity. He is interrupted by President Eden who releases you and asks you to meet him once you have retrieved your equipment from the locker in your cell. 
Exiting your cell, you meet an Enclave officer who lets you go if you pass a Speech, Strength or Charisma check. Even if you pass one of the checks, you are only temporarily left alone by the Enclave personel as Autumn eventually invalidates the President's orders and tells everybody to attack you. Keep killing the Enclave soldiers and follow your quest marker until you arrive at a room with two sentry bots, still under command of Eden, who finish off the two Enclave guards. At this point, make sure you have grabbed the Bobblehead: Energy Weapons and proceed. You enter a room with a long staircase, at the top of which you encounter President Eden - who might not be exactly like you imagined. 
Eden informs you of his plan to "cleanse" the Capital Wasteland of the mutation and disease which has gripped it by using a modified version of the FEV virus to kill any mutated or irradiated beings living in the Wasteland. The president does not let you leave without taking the modified FEV, you can however convince (or force) him to self-destruct by various means if you so desire. 
If you make Eden self-destruct,the robots in the subsequent hallways turn on the Enclave soldiers, if you do not (and refuse to put the FEV in the purifier) you have fight security bots and soldiers alike. Once outside you observe a large force of vertibirds leaving the base. If Eden's self destruct is activated, the base explodes and the tunnel is blocked with rock; there is no way back inside. At this point you meet Fawkes who is taking care of some Enclave soldiers. If you have positive karma, you have the option of asking him to join you. 
Make your way back to the Citadel where you walk in on a meeting of Elder Lyons, Scribe Rothchild and Lyons' Pride. 

Take it Back!
 
Time to take back Alaska from those rotten commies - that's what the giant robot paving your way seems to believe at least. After your return from Raven Rock, the Brotherhood of Steel decides it has to take Jefferson Memorial back from the Enclave, especially since the G.E.C.K. is now in their opponent's posession. Fortunately, Scribe Rothchild and Dr. Li have managed to reactivate Liberty Prime just in time. Following in its footsteps, Lyons' Pride and you are to assault Jefferson Memorial in hopes of regaining control over Project Purity. 
Simply follow the robot and watch it lay waste to the Enclave troops, their force fields and vertibirds. All you have to do is take care of the occasional enemy who manages to escape the wrath of Liberty Prime and the Lyons' Pride until you arrive at the Memorial. Fight the soldiers here and go inside. After making your way to the control room, you encounter Colonel Autumn whom you can either kill or make leave by passing a Speech check. 
Sweet victory! Or not... Dr. Li informs you that Project Purity sustained damage during the assault and needs to be activated immediately, otherwise it is going to explode. Unfortunately, whoever activates it is not going to survive. Now you can either run away, sacrifice yourself or make Sarah Lyons go in and activate it. Provided you go in yourself and still have the modified FEV, you can also choose whether you want to inject the virus prior to activation. In case you have not figured out the activation code yet, it's 2-1-6-Enter (Revelations 21:6 is your mother's favorite bible verse). 
Either way, the game ends here and you get to watch the ending. 
Note: The game ends immediately after the completion of this quest.