When she was a deeply troubled teenager, Nikita was rescued from death row by a secret U.S. agency known only as Division, who trained her as a spy and assassin. Nikita was eventually betrayed by the only people she thought she could trust. Now, after three years in hiding, Nikita is seeking retribution and making it clear to her former boss, Percy and her former friends Michael and Birkhoff that she will stop at nothing to expose and destroy their covert operation. Division continues to recruit and train other young people, among them Jaden and Thom, erasing all evidence of their former lives and turning them into cold and efficient killers. One of these new recruits, Alex is a beautiful girl with a violent past and a story not so different from Nikita's. The recruits all spend part of their training with Amanda, a master manipulator who can turn any ugly duckling into a swan and any bleeding heart into a killer.

Percy and Michael take their latest assignment, a Slavic leader wanted for war crimes, into protective custody. Nikita learns of their hideout and attempts to thwart their plan, but a mysterious group of mercenaries in search of nuclear material beats her to the task. Alex is activated earlier than expected for a special assignment that throws her into the crossfire of bullets. A flashback reveals a pivotal moment in Nikita's life.

Alex informs Nikita that Division is sending her on her first mission to kill the leader of a crime syndicate. Alex is uneasy about taking someone's life but is reassured by Nikita who insists on helping her with the kill order. Birkhoff informs Percy and Michael when he discovers the shell program that a Division mole has been using to connect to Nikita in the outside world. When the mission doesn't go as planned, Nikita makes a quick decision in an effort to clear Alex's name. Inside Division, Jayden attempts to reveal Alex as the mole but Thom steps in and a shocking accident clears her name.

Percy makes a move to take over the CIA, Alex goes rogue, and Michael gets trapped inside Division making him unable to help Nikita, who may have to pay with her life for helping Alex.

Nikita and Michael plot to take down Division and Oversight and are prepared to use the contents of the black box to do so. Amanda is now running Division but Oversight has assigned one of their own, a new agent named Sean, to keep an eye on her. Amanda's first mission is to get back the black box from Nikita, and she enlists Alex's help to do so. Alex refuses until Amanda tells her she will help her find the man who killed Alex's father. Meanwhile, Nikita and Michael find help from an unlikely ally.

Ryan takes charge of Division with Nikita by his side. Their first mission under the new regime is to bring in “The Dirty Thirty,” the rogue agents who failed to respond to the Division recall after Percy was killed. Unfortunately, their first mission doesn’t go as planned and Michael is arrested, forcing Nikita to change gears and hatch an escape plan for him. Alex reprises her alter ego, the spoiled Russian princess Alexandra Udinov, in a very unique way as part of the plan to spring Michael. Meanwhile, Birkhoff struggles to maintain a working relationship with Sonya, despite his growing attraction to her.