Caretaker android Markus and his owner return home and alert the police of a suspected burglary. In confronting the perpetrator, Markus bypasses his programming, thereby becoming a deviant android with full autonomy, leading the police to shoot him at arrival. Markus awakes in a landfill of broken androids and, after escaping, discovers Jericho, a wrecked ship and safe haven for deviants.

There, Markus rallies the others to fight for their rights. They perform several acts of civil disobedience, which catch the public's attention and get more androids to join. This culminates with the FBI attacking Jericho. If he survives, Markus and the others set up a final march, resulting in either a war breaking out or the president opening peace talks. Police investigator android Connor is sent by the CyberLife corporation to assist Lieutenant Hank Anderson, an alcoholic who hates androids. In the course of their investigation into an outbreak of deviants, they either bond or fall apart, potentially resulting in Hank committing suicide.

During his hunt for Markus' group, Connor starts to deviate, but can also preserve his programming. He eventually locates Jericho, where he can become a deviant himself. If he defects, Connor infiltrates CyberLife Tower and converts all androids there into deviants. If not, he attempts to snipe Markus during the final protest, but is stopped by a SWAT team or Hank. If peace is achieved, Connor can choose whether or not to shoot Markus during a speech.

Kara, a housekeeper android for Todd Williams and his daughter Alice, escapes with her after he attacks them and leaves Kara a deviant. The two travel across Detroit, intending to enter Canada, which has no specific laws involving androids and where they will be safe. Kara and Alice befriend another android named Luther along the way, who joins them on their journey. They seek the aid of an android sympathiser, who points them to Jericho to obtain passports.

They get caught up in the attack, which may result in Luther, Kara, and Alice's deaths. Kara also learns that Alice is in fact an android, replacing the daughter taken away by Todd's wife. They can reach Canada by bus or boat, survive a recycling centre, or in either case die trying.