Ninety-seven years ago, nuclear Armageddon decimated planet Earth, destroying civilization. The only survivors were the 400 inhabitants of 12 international space stations that were in orbit at the time. Three generations have been born in space, the survivors now number 4,000, and resources are running out on their dying "Ark". Among the 100 young exiles are Clarke, the bright teenage daughter of the Ark's chief medical officer; the daredevil Finn; the brother/sister duo of Bellamy and Octavia, whose illegal sibling status has always led them to flaunt the rules, the lighthearted Jasper and the resourceful Monty. Technologically blind to what's happening on the planet below them, the Ark's leaders - Clarke's widowed mother, Abby; Chancellor Jaha; and his shadowy second in command, Kane - are faced with difficult decisions about life, death and the continued existence of the human race.
Having discovered that Jasper may still be alive, Clarke, Bellamy, Octavia, Finn and Monty set out on a mission to locate their friend and are shocked at what they find. Meanwhile, on the Ark, Abby is determined to get to Earth, and enlists Raven to craft an escape pod.
In a desperate attempt to treat Jasper's festering wounds, Clarke, Finn and Wells set out in search of a seaweed antibiotic. Bellamy and his crew go hunting for food, and are joined by Charlotte, a lovable 13-year-old, who feels safe under Bellamy's protection. A thick, acidic fog appears, forcing Clarke, Finn and Wells to seek shelter inside an ancient van. While they are trapped, Clarke confronts Wells on his betrayal that resulted in her father's death.
After the shocking death of one of their own, Clarke and Finn grow closer as they try to figure out a way to communicate with the Ark. Bellamy must keep the group from turning on one another as life on Earth takes a desperate turn. Meanwhile, Abby risks having herself floated in order to give Raven the chance to stow-away in the escape pod bound for Earth.
Clarke's newfound romance with Finn is threatened. Octavia suffers a blow to the head and wakes up to find a Grounder watching her. On the Ark, Abby exposes Kane's plan to reduce the population of the Ark. Jaha and Abby notice a signal and realize at least some of the 100 must still be alive on Earth.
Bellamy leads a rescue party for Octavia that crosses the boundary into Grounder controlled forest. Flashbacks document Octavia's life aboard the Ark and Bellamy's responsibility for her. The flashback also reveals the traitor behind Bellamy's attempt on Chancellor Jaha's life.
Clarke and Raven make contact with the Ark, and Abby guides Clarke through a dangerous procedure in a desperate move to save one of their own. Meanwhile, on the Ark, Abby is removed from the council, and former Chancellor Diana Sydney takes her place. Jaha reveals to Abby that there are not enough drop ships for everyone on the Ark to go down to Earth, and Kane begins to deal with his guilt over his recent decision.
Clarke and Bellamy go on a mission to find supplies for approaching winter. Some of the 100 accidentally eat nuts with powerfully hallucinogenic properties and lose their grasp on reality. Meanwhile, Octavia seizes the opportunity to help a friend escape, and a terrifying event brings Clarke and Bellamy closer. On the Ark, Commander Shumway secretly assigns one of the 100 to hug one of his own, and the treacherous actions of Diane Sydney are revealed.
Clarke and Finn attempt to broker peace with the Grounders but all hell breaks loose when Bellamy, Jasper and Raven show up armed and ready for battle. Octavia and Lincoln grow closer. Meanwhile, tragedy strikes during the Unity Day celebration on the Ark.
Murphy returns to camp claiming to have been held captive and tortured by the Grounders, and Clarke and Bellamy have very different opinions on how to handle his return. Octavia sneaks away to find Lincoln and returns with a serious warning for the 100. Meanwhile, a mysterious virus strikes camp forcing many to be quarantined, and Jasper pulls off a heroic move.
With a low food supply at camp, Clarke and Finn lead a group out to hunt for food and wind up in a compromising position. With Finn's life in danger, Clarke makes a game-changing decision. Meanwhile, Raven makes Bellamy an offer he can't refuse. On the Ark - Kane risks his life and is reunited with Chancellor Jaha and Abby.
Clarke and Finn escape one dangerous situation only to find themselves faced with a new enemy. Bellamy makes a heroic move to save Jasper. Raven faces a new danger, and Murphy finally gets his revenge. Meanwhile, those remaining on the Ark are coming to terms with the inevitable.
Clarke pleads with Bellamy to do the right thing as conflict on the ground comes to a head. Bellamy forces Octavia to make a difficult decision. Raven and Jasper work against time and Finn makes a bold move. Meanwhile, the situation on the Ark comes to a stunning conclusion.