Andromache of Scythia, known as Andy (played by Charlize Theron), is a centuries-old warrior who, alongside her comrades Booker (Matthias Schoenaerts), Joe (Marwan Kenzari), and Nicky (Luca Marinelli), possesses incredible regenerative healing abilities. These steadfast mercenaries utilize their extensive experience to take on missions aimed at helping those in need. However, they break their own rule of collaborating with the same employers only once when they accept a task from former CIA operative James Copley (Chiwetel Ejiofor) to rescue a group of kidnapped girls in South Sudan. Copley persuades Andy and Booker that if they don't act swiftly, the girls will vanish forever.
Unfortunately, during their mission, the group falls into a trap; there are no hostages, and they are ambushed, resulting in their temporary demise. They swiftly recover and retaliate against their attackers, only to discover that Copley had orchestrated the ambush while recording their miraculous regeneration. Alarmed that the CIA might have knowledge of their powers, Andy resolves to confront Copley.
In a separate narrative thread, Nile Freeman (KiKi Layne), a U.S. Marine stationed in Afghanistan, sustains a fatal throat injury during a military operation but astonishingly heals without a trace. This triggers a series of dreams among the immortals, alerting Andy to Nile’s existence—a significant event after centuries of no new immortals. Determined to protect Nile, Andy locates and extracts her from Afghanistan, preventing military personnel from subjecting her to further scrutiny.
Meanwhile, Copley presents footage of the ambush to Steven Merrick (Harry Melling), a pharmaceutical executive intent on exploiting the immortals' gifts for personal gain. Under Merrick's orders, operatives led by Keane (Joey Ansah) are dispatched to apprehend the group. Merrick’s right-hand, Dr. Meta Kozak (Anamaria Marinca), is particularly driven to study the immortals' DNA for her research.
After a series of tumultuous events, Andy brings Nile to a safe house in France, where she introduces her to the rest of the team. There, they share their stories and disclose a grim truth—they are not truly indestructible, as their healing abilities can cease without warning. They recount the fate of an earlier immortal, Lykon, who experienced this loss, and Andy reflects on the anguish surrounding Quynh (played by Thanh Van Ngo), the first of her comrades, who was condemned to an eternity of suffering after being imprisoned at sea.
The tranquility is shattered as Merrick’s forces launch a surprise attack, resulting in Joe and Nicky being taken captive. Andy, fighting to defend her team, is wounded and discovers that her regeneration has become dormant, placing her life in peril. In a series of betrayals and revelations, Booker, attempting what he believes to be a mercy, turns on Andy and shoots her, fearing that suffering may be the only escape from their immortal existence.
As circumstances shift and Copley’s moral compass wavers upon witnessing Merrick's brutal intent to exploit the immortals, Nile escalates the situation. She seeks Copley’s assistance, unveiling Booker’s treachery in the process. Driven by the desire to rescue her newfound allies, Nile orchestrates an audacious plan at Merrick's London headquarters. With the team's combined strength, they liberate one another and fight their way out, culminating in an explosive confrontation where Nile avenges Andy, defeating Merrick.
For his betrayal, Booker is condemned to solitude for a century, cut off from the group. Nevertheless, the resolute team, fueled by their enduring purpose, entrusts Copley with safeguarding their secret and aligning them with meaningful missions around the globe. Time passes, and six months later in Paris, a disheartened and intoxicated Booker is shocked to encounter Quynh, reigniting the hope for their past.
