On the eve of the worst crisis in human history, Congresswoman Jennifer Brown clashes with the President. Her children Yorick and Hero reach an emotional crossroads. None of them know their lives are about to change forever.

After a mass casualty event wipes out every creature with a Y chromosome, President Jennifer Brown responds to the crisis. Yorick fears he may be the only survivor. Hero attempts to right a wrong.

With Jennifer and Yorick reunited, Agent 355 pitches a plan for what comes next. The dead President's daughter, Kimberly, circles Jennifer's secret. Meanwhile, Nora Brady and her daughter Mack say goodbye to home.

Yorick and Agent 355 search for Dr. Allison Mann in war-torn Boston. Back in D.C., Jennifer hides the truth about Yorick from her political rivals.

Yorick, Agent 355 and Dr. Mann hit a snag on their way to San Francisco. As the search for 355 heats up, Jennifer clashes with former cabinet secretary Regina Oliver, who has her eyes on the presidency. Hero is seduced by a charismatic leader, Roxanne, as Sam and Nora grapple with their place in a dangerous group of survivors.

Kimberly uncovers a secret. 355 and Allison reach an understanding. Yorick stumbles upon a mysterious town where things are not what they seem.

As tensions at the Pentagon come to a head, Jennifer faces a threat. The Amazons hit the road.

As the Amazons close in on Marrisville, Nora reaches a breaking point. Yorick makes a new connection while 355 faces her past.