The series is set 97 years after a devastating nuclear war wiped out almost all life on Earth. The only known survivors are the residents of twelve space stations in Earth's orbit prior to the war. The space stations banded together to form a single massive station named "The Ark", where about 2,400 people live. Resources are scarce and all crimes, no matter their nature or severity, are punishable by death ("floating") unless the perpetrator is under 18 years of age. After the Ark's life-support systems are found to be critically failing, 100 juvenile prisoners are declared "expendable" and sent to the surface in a last ditch attempt to determine if Earth is habitable again in a program called "The 100", for which the show is named. The teens arrive on a beautiful planet they have only seen from space. Confronting the dangers of this rugged new world, they struggle to form a tentative community. However, they discover not all humanity was wiped out; some people on Earth, called grounders, survived the war, and there are even more dangers lurking – Reapers and Mountain Men.
In the second season, people from Mt. Weather aid several survivors after the battle at the end of the first season. Mt. Weather is filled with residents who are technologically advanced, but unable to leave their bunker due to radiation fears. While appearing outwardly extremely friendly and welcoming, they harbor dark secrets.
After crashing on Earth, survivors from the Ark try to establish a new home, all the while searching for their lost children (the 100) and dealing with threats from the grounders. Jaha, the remaining survivor on the Ark, finds a way to leave, but ends up in the ruins of New York.