The series follows a group of post-apocalyptic survivors, chiefly a group of criminal adolescents, including Clarke Griffin (Eliza Taylor), Finn Collins (Thomas McDonell), Bellamy Blake (Bob Morley), Octavia Blake (Marie Avgeropoulos), Jasper Jordan (Devon Bostick), Monty Green (Christopher Larkin), Raven Reyes (Lindsey Morgan), John Murphy (Richard Harmon), and Wells Jaha (Eli Goree). They are among the first people from a space habitat, the Ark, to return to Earth after a devastating nuclear apocalypse. Other lead characters include Dr. Abby Griffin (Paige Turco), Clarke’s mother; Marcus Kane (Henry Ian Cusick), a council member on the Ark; and Thelonious Jaha (Isaiah Washington), the Chancellor of the Ark and Wells’ father.

Ninety-seven years after a devastating nuclear apocalypse wipes out almost all life on Earth, thousands of people now live in a space station orbiting Earth, which they call the Ark. Three generations have been born in space, but when life-support systems on the Ark begin to fail, one hundred juvenile detainees are sent to Earth in a last attempt to determine whether it is habitable, or at least save resources for the remaining residents of the Ark. They discover that some survived the apocalypse: the grounders, who live in clans locked in a power struggle; the Reapers, another group of grounders who have been turned into cannibals by the Mountain Men; and the Mountain Men, who live in Mount Weather, descended from those who locked themselves away before the apocalypse. Under the leadership of Bellamy and Clarke, the juveniles attempt to survive the harsh surface conditions, battle hostile grounders and establish communication with the Ark.

In the second season, forty-eight of the remaining detainees are captured and taken to Mount Weather by the Mountain Men. The Mountain Men are transfusing blood from imprisoned grounders as an anti-radiation treatment as their bodies have not adapted to deal with the remaining radiation on Earth. Medical tests of the forty-eight show their bone marrow will allow the Mountain Men to survive outside containment, so the Mountain Men begin taking the youths’ bone marrow. Meanwhile, the inhabitants of the Ark have crash-landed various stations on Earth and begin an alliance with the grounders to save both their people, naming the main settlement at Alpha Station “Camp Jaha”. The season ends with the massacre of the Mountain Men to save the prisoners. During this time, former Chancellor Jaha leads a group in search of a fabled “City of Light.” Jaha discovers an artificial intelligence named A.L.I.E. while John Murphy finds an alarming video implying a connection between the AI and the destruction of the world.

In the third season, Alpha Station renamed Arkadia, comes under new management when Pike, a former teacher, and mentor on the Ark, is elected as chancellor and begins a war with the grounders. Pike kills an encampment of grounder warriors while they sleep, which further damages their already fragile relationship with the grounders. Furthermore, the grounder leader Lexa is killed by her mentor during a failed assassination attempt on Clarke. A.L.I.E. – who was commanded to make life better for mankind – is revealed to have responded by solving the problem of human overpopulation by launching the nuclear apocalypse that devastated Earth, and begins to use ingestible computer chips to take control of peoples’ minds. A.L.I.E. is ultimately destroyed by Clarke, but not before warning of an impending apocalyptic disaster.