James was born in 2226. Later in his life he formed or met a group of scientists. One of them was Dr. Madison Li and another was Catherine, the love of his life. The group had one goal, to provide clean, free water for the Capital Wasteland, and was soon dubbed Project Purity. James was the chief scientist and leader of the project. It intended to purify all the water in the Tidal Basin at once. However, when his wife died after giving birth to the Lone Wanderer, he left the project to its fate and traveled to Megaton with the help of Star PaladinCross. He then asked for entry for himself and his child into Vault 101 in return for becoming the Vault's new physician, and the overseer granted his request.
Upon being accepted by the Overseer into Vault 101, James becomes the Vault's new physician due to his extensive medical knowledge and training. James never warmed up to the totalitarian state of the vault, his only wish was to return to the Wasteland to bring clean water to the people of D.C. However, because of his love for his child, he decided to stay, raising his child until they became of age. Never forgetting this mission or his deceased love, he reminds himself of her and his mission to give purified water to the Wasteland through his love's favorite biblical quote, Revelation 21:6, which he framed and hung in his living quarters and office in the Vault. He went through great lengths to ensure his child's happiness, from throwing him or her parties even to giving him or her a BB gun that his best friend found in the reactor room, which he fixed using parts from Butch's switchblade.
In 2277, James planned to return to the surface, leaving his child in the Vault to be safe. His assistant and friend Jonas distracted the guards so he could escape and therefore the Overseer had Jonas killed. Despite James' plans, the Lone Wanderer escaped the Vault and followed his trail. James first went to the small town of Megaton to visit Colin Moriarty, who he had met nineteen years ago on his way to the Vault. He asked Colin what's been happening in the wasteland since then and Colin told him about Galaxy News Radio. James left in a hurry and managed to make his way through the ruins of Washington, D.C., and reached the GNR building plaza, where he talked to Three Dog. He told James what had been happening recently in the wasteland, and then James left to find Dr. Li. Arriving at Rivet City, he asked for Madison's help to restore the project but she declined. Then he headed off to the old lab at the Jefferson Memorial. James soon found out he needed a Garden of Eden Creation Kit. He marked his way to Vault 112 to find Stanislaus Braun, the creator of the G.E.C.K., and to learn more about it. James arrived at Vault 112 and entered the Tranquility Lane simulation. He talked with Braun but didn't want to play any of his games, so Braun trapped him in the body of a dog named "Doc." The Lone Wanderer arrived in Tranquility Lane and soon frees their father. After a talk, the two return to Rivet City. At Rivet City, James successfully recruits Madison Li and her team and they head to the Jefferson Memorial. After arriving at the memorial, the scientists soon get things back on track, but then the Enclave arrive.
Augustus Autumn entered the facility under guard of Enclave soldiers. The activation room has been locked and Autumn begins to threaten James, demanding he hand over the activated Project Purity. James explains that the project isn't yet functional, but then, after the other scientist in the room is shot and killed, James submitted and caused a disruption within the activation room. This caused a massive radiation leak that killed everyone in the control room with the exception of Autumn. James then collapses and dies of radiation poisoning, telling his child "Run. Run!".
Baby Steps: James puts the one-year old Lone Wanderer in a playpen in their room which contains the You're S.P.E.C.I.A.L.! book. After a brief absence, James returns and shows the child their mother's favorite Bible quotation, and takes his child to see Amata.
Growing Up Fast: James has a small conversation with the Lone Wanderer at the beginning of their tenth birthday party, and later in the party gives them a BB gun as a birthday gift, and tasks them with killing a radroach.
Escape!: James' unexpected absence from Vault 101 prompts a security crisis and propels the Lone Wanderer out into the wastes.
Following in His Footsteps: The Lone Wanderer searches for their dad. They can either go straight to Vault 112 (where he is being held); or they can follow the quest line, by going to Megaton, which directs them to Galaxy News Radio, which directs them to Rivet City, which directs them to the Jefferson Memorial which then leads them to Vault 112.
The Waters of Life: Father and child make their way first to Rivet City, then to the Jefferson Memorial, the site of Project Purity. As the Enclave storms the Memorial, James refuses to cooperate with Colonel Augustus Autumn. In the end, James floods the room with radiation, attempting to kill Autumn but killing himself in the process and with no success in his objectives.
When the player is doing tasks to make Project Purity work, James will say that he heard of the player's actions. His reaction will change depending on how you resolved the Power of the Atom quest. If you disarmed the bomb, he will ask you if you truly did it, and will be proud of you if you say that you did. If you caused Megaton's destruction and admit it to James he will be disappointed (you can lie to him, but he won't really believe you unless you have very high Karma).
If you did not resolve the Power of the Atom quest at all, or if you talk to him again after he comments on the aforementioned quest, he will instead comment on your current Karma level. If you have good Karma, he will say "You're a good person, and it shows." If you have bad Karma, he will instead comment on how you "seem troubled, like there is a cloud hanging over you." If you have neutral Karma he will simply greet you in the default manner.
Birth scene: James delights over the birth of his child, presenting the child to his wife, who expresses pride and happiness before going into cardiac arrest. James then tries, to no avail, to save her.
James counts as a "companion", and as such will use up ammunition on any non-companion weapon (unlike most non-player characters, who have infinite ammunition).
Neither James' nor Catherine's surnames are known or stated in gameplay, thus allowing players the freedom to make up their own surname.
It seems that James has a preference for Scotch. According to Project Purity personal journal #5, he mentions having downed "half a bottle of Scotch" the night he broke into the Overseer's computer. When visiting his living quarters at Project Purity, the player can find a number of empty Scotch bottles around James' living area.
After freeing him from the Vault 112 simulation, the player can ask their father whether he enjoyed being a dog. James humorously replies that it "had its moments" but that he missed "having opposable thumbs."
In Vault 101 he has the same hair color as the Lone Wanderer, but in the Wasteland, his hair is gray-white due to aging.
The unused skin of Doc seems to be a German Shepherd, considering Stanislaus Braun is German. Also, it seems that the dog has different eye color - similar to Dogmeat.
James may not follow to the Jefferson memorial if you fast travel.
The Lone Wanderer can show their contempt and hatred for James by saying to him "Fuck you, Dad." Also, when Star Paladin Cross asks about him, the player can say that he "lived as he died, as a selfish asshole." Yet James simply says he's "sorry you [the player] feel that way" about the former.
James is voiced by actor Liam Neeson, after whom the character is also physically modelled. "This role was written with Liam in mind, and provides the dramatic tone for the entire game. "Liam is absolutely amazing to work with," said Todd Howard, Executive Producer of Fallout 3. "It’s been a pleasure bringing the father to life and working with the wonderfully talented people at Bethesda on Fallout 3," said Neeson. "I hope the fans of the franchise and the game will be excited by the results."
At one point in development, the story of Fallout 3 was different, and James would have become a super mutant. 
ps3xbox360 On the way back to Rivet City from Vault 112, he will sometimes get stuck while traveling with him. If this occurs, fast travel to Rivet City and wait 24 hours in the Science Lab. He will appear and start talking to Doctor Li. [verified]
ps3xbox360 James might disappear if you fast travel to the Jefferson Memorial from Vault 112. [verified]