Prequel

In the beginning, the player is selected as a replacement player for the "Patriots" team, on the night of the championship game of the 2260 season of the "Vault Ball" sport. During the match, the player can choose to Tackle (Path of the Warrior) or Dodge (Path of the Scientist). Depending on the choice, the player is next in Coach John Bragg's Office (Tackle), being praised for winning the game and offered a job in the Vault's security force, or in the Vault Infirmary (Dodge), waking up from being injured and losing the game, with a broken leg. As a Warrior (Tackle), the player may ingratiate themselves to Coach Bragg and his sister Chevy, the Vault Security lieutenant, thus gaining a spot in Vault Security and potentially also Bragg's special "Patriot" vault defense training program. If they fail to do so, they will instead be sent to join the Vault's maintenance team. As a Scientist (Dodge), the player is given the option to help Dr. Rossman, the vault's robotics expert, repair the vault's computer mainframe, extracting information on the history of the vault and the player character along the way. Concurrently, the player may interact with other vault residents, with some interactions determining who will or will not become a potential companion for the later installment. This section is ended at any time when the player chooses to go to sleep in their home apartment.

While the player sleeps, John and Chevy Bragg are revealed to be members of the Enclave who have used their Patriots program to indoctrinate the young vault residents into loyal Enclave soldiers. Forced to accelerate their plans for the vault, they begin a revolt, causing an explosion which collapses parts of the lower levels.

Chapter 1

The player wakes up, finding their siblings dead and their home destroyed, while the vault security forces and Enclave Patriots fight outside. The player may choose to side with Vault Security to defend the vault, or join the Enclave if their relationship with Bragg is good enough. After helping either side to gain the advantage, the player confronts the overseer and learns that he has set the vault to self-destruct. They are then told to gather their remaining allies and evacuate, and the chapter ends upon reaching the gate to the outside world beyond the vault cavern.

Chapter 2

This chapter focuses on the player's escape from the vault before its destruction and the night that follows, during which the player is told to consider where to seek refuge in the wasteland: Union City, a makeshift township where the NCR houses its regional command, or Athens-Tec Mine, the seat of the Raider Alliance's power.

Chapter 3

This chapter focuses on the player's mysterious past, as well as their role in the conflict between the regional powers as direct warfare breaks out for control of the Pass. The player becomes a special agent for their respective faction via General Silverman or Elsdragon, working to undermine the opposing side (or potentially even undermining both sides as an undercover Enclave infiltrator.) They may also work with Senator DuVille to further the Bishops' interests or collude with Kieva Nanjima to try and overthrow Elsdragon.

Regardless of affiliation, the player is eventually sent to scavenge a pre-war military base named Fort Daggerpoint, meeting a mysterious mercenary named Annai Oran in the process. This is revealed to be a trap set by an army of super mutants called the Unity, remnants of the Master's Unity from the original Fallout, who claim that the player has a special destiny and attempt to coerce them to join their master plan. If the player escapes, they are then tasked with assassinating the opposing faction's leader, with variations depending on whether or not the player chooses to help Senator DuVille or Kieva Nanjima instead. Finally, the player is sent to fight their way through Fort Daggerpoint, where it is revealed that Colonel Bragg's Enclave force has also been hiding, to defeat the mutant and Enclave threat, or to regroup with Bragg's forces as an Enclave-affiliated player. In the depths of the fort, the player confronts the Father, the Unity's leader, who reveals that the player was a clone created by the Unity, possessing a parasite from a pre-War government experiment codenamed "Project Brazil" which gives them special regenerative powers. The Father engineered the adoption of the player into Vault 18 as a means of ensuring they would safely mature, and intends to use the player's fully developed parasite to fulfill the Master's original plan for humanity. After dealing with the Father, the player encounters Annai Oran, who confirms the player's origins and reveals that she is actually a mutant who possesses a defective version of the Project Brazil parasite, and that the Bragg siblings are clones of her created via the parasite's defect. Alternatively, the player regroups with Colonel Bragg as an Enclave infiltrator before they are attacked by Oran. The player either helps Annai defeat her clones, during which she sacrifices herself to end the threat of Project Brazil, or helps the Braggs eliminate Oran to consolidate their victory.

Endings

In the majority of endings, the player is tasked with deciding whether to destroy Fort Daggerpoint or secure it for their faction. If the player assisted the Enclave, they instead use the fort's nuclear missiles to devastate the NCR and head east to regroup with other Enclave elements. Regardless of faction choices, the Unity is exterminated and the Raider Alliance is eventually forced out of the Pass, allowing the NCR to unify California. The player ultimately falls out of contact with their faction, prompting them to start over as a courier. During this time, they inadvertently destroy the settlement of Hopeville and lose their parasite's powers as a result, leading into the events of Fallout: New Vegas.

There are also two independent endings which do not continue the player's story into Fallout: New Vegas. These occur if the player opts to join the Unity and fulfill their plan, or if the player kills the leaders of every major faction, with the implication that as a functionally immortal entity with nothing to hold them back, they will ultimately go on to eradicate all life on the planet.