The fifth and final season brings Sarah and the sestras to their darkest days in an effort to finally cut off the head of the snake and win their freedom. Throughout the season, the sisters individually delve into their past to confront personal struggles and emerge stronger through these self-explorations. Despite the great risk to attain freedom for themselves, their families, and the host of clone sisters they’ve yet to meet, clone club uncovers the missing pieces of the insidious conspiracy and finally learn the story behind their origin.
Sarah is deeply wounded and struggling to stay alive on the Island. Driven deep into its forest by Neolutionists and worse, she strives to make it far enough to rescue Cosima. Meanwhile, a recovering Cosima reunites with Delphine, but there's way more going on on this Island than Cosima imagined and Delphine can't give her all the answers she needs. What is clear is that Rachel is now firmly in charge as the right-hand of the 170-year-old founder of Neolution, P. T. Westmorland. Back home, Neolution puts the screws to Alison and Donnie in their hunt for Helena. The sestras couldn't be further apart when they need most to be together.
Captured by Neolution Sarah receives a damning ultimatum from Rachel: come into the fold, or lose your family. Her decision causes a clash with Kira who begins exploring her own maturity. Meanwhile, Ferdinand struggles to get a handle on Rachel's new velvet glove mandate in pursuit of the clones. With Neolutionists and Ferdinand watching their every move, Felix brings an old ally into the mix to help his family get Kira to safety. On the Island, Cosima struggles to comprehend the reality of the Neolution myth made real.
Stuck on the sidelines with Neolutionists crawling all over her home, Alison seeks to return to her community center, but Bailey Downs has moved on from her. As she flounders to take back some semblance of control, the ghost of friendships' past rears its handsome head. Art and his new partner show up at the Hendrix residence to continue their search for Helena, forcing Art to make a difficult moral judgement.
Following up on intel from a mysterious source, Mrs. S heads on the road with Sarah to investigate a lead on a Neolution defector. Meanwhile, an unexpected reunion takes place on the island, while Cosima's research leads her to a discovery more terrible than she could have ever imagined. As more pieces slide into place, the puzzle only seems to become more complicated.
While Sarah and Kira spend some well-needed bonding time at home, secrets are unlocked about Kira’s special gifts that are surprisingly linked to the island’s creature. Meanwhile, Cosima joins Delphine at the mansion for a twisted family dinner, causing a dangerous showdown with the Neolution patriarch.
Cosima is forced into an alliance when an old enemy returns to the island, accelerating P. T. Westmorland's sinister agenda. Meanwhile, on the mainland, Krystal stumbles onto a vital clue to the Neolution endgame. Sarah and Mrs. S’s research into Neolution's corporate ties leads to the cosmetics industry and an inevitable cross with Krystal Goderitch. But before Sarah can dig deeper, Krystal hijacks the investigation.
As P. T. Westmorland demands a more aggressive action on Kira, and Sarah fights to save her daughter, Rachel discovers a dark secret that makes her question her place within Neolution. Meanwhile, Cosima has returned with a vital clue to Westmorland's true identity.
Mrs. S orders the sisters to take a night off from sleuthing to celebrate Felix's art opening. But while Felix attempts to impress a famous gallerist with the help of his sestras, Sarah remains on edge with a nagging suspicion that S is hiding something. Meanwhile, wounded and desperate, Rachel reunites with an old ally, but their plans for revenge on Neolution put Clone Club in the line of fire.
A devastating loss is eclipsed when word reaches Sarah that Helena has been kidnapped. Clone Club bands together in a race against time, determined to find her before she has her babies. And with time running out, Sarah is forced into action in a last-ditch effort to save her sestra.
With Helena forced to take shelter behind enemy lines, it’s a bloody last stand for survival as Sarah and Art struggle to protect her, and end the siege on the sestras once and for all.