Mass Effect takes place in the year 2183, in a galaxy found to be inhabited by several sentient races other than humanity. The galaxy's intelligent races gather around the Citadel, an ancient space station that serves as the seat of the Galactic government.
Eden Prime
Commander Shepard is an officer of the Systems Alliance Navy, serving on the SSV Normandy. He and Lt. Kaidan Alenko, a biotic, are sent to Eden Prime, a human colony world, to unearth a Prothean beacon, an ancient artifact created by the extinct race known as the Protheans. They are accompanied by Nihlus Kryik, a Turian Spectre (an elite soldier who works with the Citadel Council to keep the peace). Shepard is under observation, as a potential candidate to become a Spectre, the first human to hold the title.
On the ground, the team meet Gunnery Chief Ashley Williams, a soldier who is also serving with the Systems Alliance. They discover that an army of robotic beings called the Geth are attacking Eden Prime, led by Saren Arterius, a highly accomplished Spectre who appears to have gone rogue. Nihlus is killed by Saren, who goes on to find and interact with the Prothean beacon.
Prothean Beacon
When Shepard touches the beacon, he receives a vision showing the massacre and defeat of the Protheans. After he has recovered, the three survivors travel to the Citadel to meet with Donnel Udina, humanity's Ambassador. With Udina's help, Shepard attempts to convince the Council to revoke Saren's Spectre status. He is initially unsuccessful, and begins to search for clues. First, he finds Garrus Vakarian, a Turian Citadel Security (C-Sec) Officer, and enlists his help, along with that of Urdnot Wrex, a Krogan Battlemaster and bounty hunter.
Proving Saren's Guilt
With their help, Shepard finds and enlists Tali'Zorah nar Rayya, a Quarian engineer who has found a recording proving that Saren has turned against the Council and is aiming to help the Reapers, a race of ancient machines that wiped out the Protheans, to return to the galaxy. Confronted with this evidence, the Council removes Saren's spectre status and grants this status to Commander Shepard. Captain David Anderson, the Captain of the Normandy, gives Shepard control of the ship.
Liara
Shepard and his squadmates travel to the planet of Therum to find Dr. Liara T'soni, a talented Asari biotic, and a leading expert on the Protheans. She is the daughter of Matriarch Benezia, who is known to be working with Saren, but turns out to be opposed to her mother and Saren, and agrees to join Shepard.
Noveria
Shepard then travels to Noveria to find Matriarch Benezia. He discovers that a race known as the Rachni, who fought a war against the other races of the galaxy many centuries ago, were imprisoned on Noveria, but have escaped. Shepard defeats Benezia, who reveals that Saren is searching for the Mu Mass Relay, and since her indoctrination by the Reapers has been broken, she tells Shepard the location of the relay.
Just before he leaves, Shepard finds the egg which will grow into the Rachni Queen. He can either destroy it to wipe out the Rachni, and prevent the Rachni Wars from ever reocurring, or leave it intact and make the queen promise never to attack the other races, leaving the Rachni as potential future allies.
Virmire
A lead found by the Council sends Shepard to Virmire, where the Salarian Special Tasks Group, led by Captain Kirrahe, has discovered a Krogan breeding facility (though the Krogan were left mostly infertile by a genophage created to end the Krogan Rebellions). Urdnot Wrex is visibly furious that Shepard wants to destroy the facility. Shepard can make peace with him, or have him killed, in which case he does not appear in future games.
The team discovers that the facility is not a breeding facility, but a facility intended to study the effects of Reaper Indoctrination. Shepard finds another Prothean beacon, which creates a hologram of Sovereign, a powerful Reaper, who explains that the organic races of the galaxy will be exterminated.
Difficult Choice
A nuke is set to destroy the base, but the Geth are attacking on multiple fronts, and both Kaidan Alenko and Ashley Williams are in danger. Shepard can only rescue one of these; the other sacrifices themself to allow the others to escape.
The Council refuses to believe that the Reapers are a threat, so Shepard acts without their authority and sends the Normandy through the Mu Relay to Ilos, the planet which Saren wanted to reach.
Ilos
On Ilos, Shepard fights through Saren's army of Geth and finds a Prothean Virtual Intelligence named Vigil. Vigil reveals that the Citadel was not created by the Protheans, as earlier thought, but by the Reapers to attract all intelligent races in the galaxy. It is, in fact, a mass relay leading to dark space, where the Reapers are waiting.
Sovereign was left behind after the extermination of the Protheans to monitor the galaxy's developing races, and summon the Reapers when it was the time to exterminate them. The Protheans were not the first race to be caught in this trap; it is revealed to be a cyclical procedure which has taken place several times already.
Vigil claims that Sovereign alone can be defeated by the Citadel's defence fleet, but if he manages to activate the relay and summon the rest of the Reapers, the sentient races of the galaxy will never be able to survive.
Showdown with Saren
Shepard returns to the Citadel to find it under attack by Saren, Sovereign and the Geth. Saren makes his way to the control room, and Shepard and his squadmates follow. Saren explains to Shepard that Sovereign has shown him a future of synthesis, in which organics are made partly synthetic to perfect them. Shepard begins to argue against him, and Saren shows signs of resisting Sovereign's indoctrination, but the implants in his brain cause him pain every time he disagrees with Shepard. Saren finally realises his mistake, but says that he cannot possibly recover, and kills himself.
Future of the Council
Shepard takes control of the Citadel, and is informed that he has control of the Alliance's Fifth Fleet. He can use this to protect the Council and save their lives, or leave them to die and order it to focus its fire on Sovereign. Although the Reaper causes enormous damage, the Alliance gains the upper hand and Sovereign is destroyed.
Three different endings are possible. If the Council was saved, it remains intact, and is so grateful that it appoints one human member - Shepard can choose either David Anderson or Donnel Udina for this position. If the Council is destroyed, the new council is chaired by a human - again, either Anderson or Udina, depending upon Shepard's choice. At this point, Shepard can choose to include other races on the Council or keep it human-only. Due to a glitch, the decision of who joins the Council is not saved, but instead re-made at the beginning of Mass Effect 2.
Epilogue
The Council finally accepts the existence of the Reapers, and Shepard sets out on the Normandy on a mission to stop them once and for all.
