Season 4 of the drama will see leader-of-the-pack, Sarah, reluctantly return home from her Icelandic hideout to track down an elusive and mysterious ally tied to the clone who started it all - Beth Childs. Sarah will follow Beth’s footsteps into a dangerous relationship with a potent new enemy, heading in a horrifying new direction. Under constant pressure to protect the sisterhood and keep everyone safe, Sarah's old habits begin to resurface. As the close-knit sisters are pulled in disparate directions, Sarah finds herself estranged from the loving relationships that changed her for the better.
A flashback to Beth Childs' final investigation, days before her suicide.
After evading a Neolution attack in Iceland, Sarah returns home to track down an elusive new ally. As Cosima struggles with Delphine’s disappearance, Alison and Donnie host a pregnant and ever-hungry Helena. Meanwhile Felix, feeling like an outsider, embarks on his own journey of self-discovery.
As Sarah reels from the shocking discovery of Neolution’s biotech, she’s desperate to find answers. Rachel receives a visit from her keeper and takes a fraught step forward towards recovery. Meanwhile, Helena is mistaken for “Mrs. Hendrix” when she answers a visit from suspicious visitors.
Sarah forms an alliance with a former enemy in hopes of getting to the head of Neolution. Elsewhere, Allison orders Felix and Donnie to invade a Neolution fertility clinic and a Susan Duncan leaves Rachel to make a devastating decision.
Sarah’s day off to reconnect with Kira quickly turns into a sleuthing mission aimed squarely at discrediting Felix’s new ties. Cosima steps up with Donnie to further investigate the Neolutionist fertility research center. While Donnie bumps into an all too familiar face, Cosima makes a shocking discovery that leads her into a dangerous encounter.
When Cosima admits doubts about finding a cure in time to save her life, Sarah makes a lone decision that exposes Kendall to those she’s spent years hiding from. Meanwhile, Art and Felix team up to protect naïve clone, Krystal Godderitch, from herself.
Sarah regresses to old habits while struggling to cope with the consequences of her decisions —reconnecting with Beth on a dark night of the soul. Back at the lab, Cosima, haunted by vicious memories and news of Delphine, attempts a dangerous Hail Mary to find a cure. At the Hendrixes, Alison is more determined than ever to create normalcy for her kids. As she forges ahead with a birthday party, Donnie is caught in the Neolution crosshairs.
As Alison is terrified by Neolution threats made against Donnie, Sarah and Mrs. S question her loyalty to her sisters. While Sarah is distracted, Siobhan sneaks out to seek vengeance. Meanwhile, Cosima and Susan Duncan work together in a final attempt to discover a cure.
With Susan Duncan deposed, Sarah finds herself in the same position as Rachel — under the heel of a new HBIC — causing the archenemies to come together for the greater good. Cosima and Susan butt heads on the ethical implications of human experiments. Meanwhile, when the Hendrixes' legal counsel, Adele, further investigates Donnie’s case, she begins to suspect Felix is keeping deep secrets. Helena’s arrival forces Felix to make a difficult decision.
In the season finale, when communication with Cosima is cut off and Neolution appears to be within striking distance, Sarah’s alliance with Rachel goes out the window. Sarah lures a high-level Neolutionist into a trap, and sets out to bring down Neolution once and for all.