In 2003, senior CIA official Fitzroy visits a prisoner. Eight years earlier the prisoner was a minor convicted of killing his abusive father to protect his brother. Fitzroy offers the man his freedom in exchange for working as an assassin in the CIA's Sierra program.

In 2021, on a mission in Bangkok, the prisoner Sierra Six, is working with fellow CIA agent Dani Miranda to assassinate a target suspected of selling off national security secrets. He is unable to do so stealthily without harming civilians and attacks the target directly, mortally wounding him. Before dying, the target reveals that he worked in the Sierra program as Sierra Four, and hands Six an encrypted drive detailing the corruption of CIA official Denny Carmichael, who is the lead agent on the assassination mission. Carmichael is elusive about the true purpose of the mission and the contents of the drive when confronted by Six, and Six refuses evacuation from Bangkok with Carmichael's men. He sends the drive to former Sierra Program handler Margaret Cahill in Prague, and calls a now-retired Fitzroy to request extraction. Carmichael hires mercenary Lloyd Hansen, an ex-CIA agent kicked out of the agency for his sociopathic tendencies, to track down Six and retrieve the drive. Hansen does so by kidnapping Fitzroy's niece Claire, forcing Fitzroy to authorize Six's murder by the extraction team. However, Six kills them and escapes.

Frustrated, Carmichael sends his subordinate Suzanne Brewer to oversee Hansen and keep him in line. Hansen keeps Claire hostage in a mansion in Croatia, where he has based his operations. Hansen also puts a bounty on Six's head to attract mercenaries and assassins to hunt him down. Six heads to Vienna to find Claire's pacemaker's serial number from Laszlo Sosa, but Sosa betrays him for the bounty. Six escapes just as Hansen arrives with his team, and is rescued by Miranda. Miranda's reputation is in tatters following the Bangkok mission and she initially plans to bring him in to salvage her career at the CIA. Six convinces her to drive him to Cahill's apartment in Prague, where she decrypts the drive, which reveals the extent of Carmichael's corruption on behalf of a mysterious benefactor working for a shadow government. Hansen sends several teams of assassins to Cahill's home, and the terminally ill Cahill blows up her home to give Six and Miranda a chance to escape.

Six is arrested and handcuffed in the square. A shootout in the streets of Prague follows killing all the police present & Six escapes on a tram. A long chase and gun battle ensues, and Six is saved by Miranda, in Cahill's bulletproof car. The two infiltrate a hospital to track down Claire through the wireless signal broadcast from her pacemaker. The mercenary "Lone Wolf" steals the drive from them, knocking them out, and brings the drive to Hansen. Six and Miranda follow the pacemaker to Hansen's base. Miranda creates a distraction while Six infiltrates the mansion and rescues Fitzroy and Claire. Fitzroy is mortally wounded as they flee and sacrifices himself in a failed attempt to kill Hansen. Miranda knocks out Hansen's men, but Lone Wolf narrowly escapes. He defeats Miranda in a fight but gives her the drive, having become disgusted with Hansen's willingness to kill children and his lack of morals.