Mass Effect 3 begins on Earth with Commander Shepard having been detained following the events in Arrival.Out of the blue, the Reapers attack and the planet is overwhelmed. Shepard escapes a burning Vancouver on the Normandy with the help of Admiral Anderson and leaves to gather help from other species while Anderson coordinates human resistance on Earth. Before leaving the Sol System, Shepard is ordered to Mars by Admiral Hackett who claims that researchers have uncovered something that may give humanity a chance against the Reapers. There, Shepard battles Cerberus forces and encounters former squad-mate Liara T'Soni, who has discovered plans for a Prothean superweapon that may be capable of defeating the Reapers. Before leaving the facility, Shepard speaks with the Illusive Man, who claims he wants to use the Prothean weapon to take control of the Reapers.
Next, Shepard heads for the Citadel. Once there, Shepard pleads for help from the Council, but they are reluctant to oblige due to their own preoccupations. Shepard realizes that the only way to gain other species' assistance will be to help them with their problems and garner favors, while at the same time gathering war assets to be used against the Reapers in battle. Eventually, Hackett begins construction on the Prothean weapon and dubs it "The Crucible".
Shepard's crew's first objective is tackling the krogan-salarian-turian conflict centered around the genophage. Afterward, they intervene in the geth-quarian war and defeat a Reaper. Finally, they attempt to defend the asari home world Thessia from the Reapers while simultaneously gathering information on "The Catalyst", an essential tool for the Crucible's effectiveness. At a Thessian temple, Shepard encounters a VI called Vendetta. As it is about to reveal information regarding the Catalyst, Cerberus intervenes and steals it. Shepard then attacks their headquarters, killing their second-in-command Kai Leng but failing to capture the Illusive Man. After regaining control of Vendetta, Shepard learns that the Citadel is the Catalyst and that the Illusive Man has been indoctrinated. Because of his indoctrination, the Illusive Man has told the Reapers of the Citadel's true identity and they have moved it to a defensive position in Earth's orbit.
Under Hackett's leadership, the galaxy's forces attack the Reapers on Earth in an attempt to retake the Citadel and use it as the Catalyst for the Crucible. Shepard helps an assault on London, the focal connection point from the planet to the Citadel. Reunited with Anderson, Shepard eventually begins the final push to the Citadel but is attacked by Harbinger. While charging toward the conduit that sends humans to the Citadel, Shepard's squadmates are injured and evacuated. Shepard continues the charge but is wounded. He barely makes it and meets up with Anderson and together they encounter an indoctrinated Illusive Man. They stop him, but Anderson is mortally wounded in the process. Shepard is then transported to the pinnacle of the Citadel where a childlike AI appears. The AI declares itself as the Catalyst and the Reapers' creator. It reveals that the Reaper cycle is an attempt to prevent organic life from wiping itself out by creating synthetic life; creators, the Catalyst argues, are always doomed to be destroyed by the created. The Catalyst characterizes the harvest as an ascendance, wherein advanced organic races are preserved in Reaper form and space is left for more primitive species to rise, evolve, and advance.
The Catalyst says that it has lost faith in the Reapers' ability to achieve their purpose and gives Shepard three options of defeating them: control the Reapers, destroy the Reapers and all synthetic life, or synthesize all organic and synthetic life together. Each choice results in Shepard's apparent death and the destruction of the entire mass relay network. London suffers varying degrees of damage and the Normandy crash lands on an alien planet. If the player's Effective Military Strength is high enough and Shepard chooses to destroy the Reapers, the game ends with a cutscene of Shepard taking a deep breath in a pile of rubble, hinting at survival. In a post-credits cutscene, an old man known as the "Stargazer" tells Shepard's story to a young boy, implying that Shepard's legend lives on
