In 1995, young Natasha Romanoff and Yelena Belova are whisked away from their home in Ohio by their surrogate parents, Alexei Shostakov (aka Red Guardian, Russia's answer to Captain America) and former Black Widow Melina Vostokoff. The girls are given to Dreykov, who puts them through the Red Room for further training.
21 years later, following the battle between the Avengers at Leipzig/Halle Airport, Natasha is labelled a fugitive by the government for violating the Sokovia Accords. She escapes from U.S. Secretary of State Thaddeus Ross and flees to a safehouse in Norway, reuniting with her contact Rick Mason. In Morocco, Yelena is still working for the Red Room. Yelena kills Oksana, a former Black Widow, only to come in contact with a substance called Red Dust, which removes the Red Room's control over her. She sends this antidote to Natasha's safehouse in the hopes that she will return to help her.
As Natasha unknowingly drives off with the antidote, she is attacked by Taskmaster, who is after the Red Dust. Natasha manages to evade Taskmaster and learns that the Dust came from Yelena. The two reunite in Budapest, but are attacked by Black Widows. While escaping, Natasha learns the Red Room is still active and that its leader, Dreykov, is still alive. In order to join S.H.I.E.L.D. years previously, Natasha's mission had been to kill Dreykov. After detonating a building containing Dreykov and his young daughter Antonia (an act that has haunted Natasha), both were presumed dead. In the present, Natasha and Yelena evade Taskmaster and meet back up with Mason, who supplies them with an aircraft.
Natasha and Yelena break Shostakov out of prison to learn where Dreykov is. He tells them that they need to speak with Vostokoff, who lives on a farm in Russia using mind control on pigs. Yelena reveals that while they were not a real family, she still wanted to believe that they were so. Shostakov and Vostokoff admit that they, too, wished they were a real family. Unfortunately, Vostokoff gives their location to Dreykov. His agents arrive and take them away to the Red Room, located on an aerial base.
As Dreykov congratulates Vostokoff for finding Natasha and Yelena, it is revealed that Vostokoff and Natasha used face mask technology to switch places at the farm, having planned their own capture. Natasha learns that Taskmaster is Dreykov's daughter Antonia, who suffered severe damage from the explosion; Dreykov was forced to put a chip in her head to help her, also turning her into the perfect soldier. Natasha discovers that she cannot harm Dreykov due to a pheromone lock he installed in every Widow. She notices that Dreykov has been controlling Widows all around the world via his control desk. After goading Dreykov into punching her in the face, Natasha manages to sever a nerve in her nasal passage to negate the pheromone, allowing herself to attack Dreykov.
Vostokoff attempts to take out the ship's engine. Meanwhile, Shostakov battles Antonia, while Yelena searches for the other Widows sent to protect Dreykov. Dreykov escapes as the Widows gang up on Natasha. However, Yelena creates a Red Dust bomb, releasing the Widows from their mind control. Natasha reaches the control desk and copies the locations of the other Widows worldwide to a portable drive, just as the Red Room begins to explode and fall. Before leaving the control room, Natasha picks up two vials of Red Dust that survived Yelena's bomb. Vostokoff and Shostakov are forced to escape the ship via aircraft just as Yelena takes out Dreykov's escape ship, killing him.
Natasha gives Yelena a parachute as she and Antonia have one final battle through the sky before safely landing on the ground. Natasha uses one vial of Red Dust on Antonia, freeing her from her mind-control. The rest of the Widows arrive as Yelena, Vostokoff, and Shostakov say goodbye to Natasha. Yelena gives Natasha her vest to remember her by, and Natasha gives Yelena the last Red Dust vial and the portable drive, instructing her to find and free the other Widows. As they leave, along with a recovering Antonia, Natasha awaits the arrival of Ross and his men. Two weeks later, Natasha, now sporting blond hair, reunites with Mason, supplying her with a quinjet. She rides off to free the detained Avengers from the Raft.
In a post-credits scene set after Natasha's death, Yelena encounters Contessa Valentina Allegra de Fontaine, now her employer, at Natasha's grave. Yelena receives her next assignment: take down Clint Barton, the man she claims is "responsible" for Natasha's death.
