In the year 2046, it's a new Earth - with new rules. Over thirty years after various alien races arrived on Earth, the landscape is completely altered, terraformed nearly beyond recognition. To the town of Defiance, on what used to be St. Louis, comes the mysterious Nolan and his charge, Irisa.

As the story of Defiance resumes, the lives of the townspeople are in drastic turmoil. The Earth Republic has assumed control of the town, with far-reaching consequences including a new mayor. Nolan traverses the badlands to find a lost Irisa, Amanda has an unexpected new role in the town as she searches for Kenya and the Tarr family desperately tries to keep control of their criminal empire in the midst of dramatic changes.

Following the events of the season two cliffhanger finale, season three of Defiance opens on the eve of an impending military siege upon the town, which has fallen on hard times following the collapse of its lucrative mines.