Still struggling with the death of her sister Natasha Romanoff, Yelena Belova continues working as the personal enforcer for CIA director Valentina Allegra de Fontaine. After infiltrating an O.X.E. research facility in Kuala Lumpur, Yelena destroys evidence linking de Fontaine to Project Sentry, a secret program designed to artificially create superhumans. Although Yelena begins questioning whether her work has any meaning, she accepts another assignment from de Fontaine.

Meanwhile, Bucky Barnes has entered Congress and is working to impeach de Fontaine over her alleged involvement with O.X.E. and its illegal experiments. De Fontaine denies everything and orders her employees to destroy any remaining evidence. In Washington, Yelena visits her adoptive father, Alexei Shostakov, who now operates a limousine service. She confides that she feels lost without Natasha and questions whether she should continue working for de Fontaine. Alexei encourages her to find a purpose beyond simply following orders.

Yelena’s next mission takes her to an O.X.E. vault in Utah, where she encounters Ghost, U.S. Agent, and Taskmaster. Each operative has been sent there for a different assignment, but their confrontation quickly becomes a deadly free-for-all. Ghost kills Taskmaster, while a mysterious, amnesiac man named Bob Reynolds becomes trapped inside the facility. As the operatives attempt to escape, they realize they have all been deliberately sealed inside the vault so de Fontaine can eliminate them and erase evidence of her involvement with Project Sentry.

The group narrowly survives an attempt to incinerate them, but Yelena experiences a disturbing vision of her past after touching Bob. As they make their way to the surface, Bob reveals his deep feelings of worthlessness, while Yelena admits that she has spent much of her life suppressing her own pain. De Fontaine and her assistant, Mel, discover that Bob is actually Robert Reynolds—the sole surviving test subject of Project Sentry.

When O.X.E.’s strike team arrives, Yelena, U.S. Agent, Ghost, and Bob fight their way out of the facility. Bob unexpectedly demonstrates incredible powers, surviving a barrage of gunfire before taking flight and crashing back to Earth. After escaping with the Project Sentry documents, the group is rescued by Alexei, who arrives in his limousine. During their escape, Yelena jokingly refers to the unlikely group as the “Thunderbolts.”

Bucky eventually tracks them down and detains the group, intending to use their testimony against de Fontaine. Meanwhile, O.X.E. takes Bob to the Watchtower, formerly Avengers Tower. De Fontaine manipulates him into becoming the superhero Sentry, hoping to use his powers to prove her innocence and eliminate anyone who threatens her position. When the Thunderbolts confront her, she unveils Sentry as Earth’s newest superhuman champion and orders him to destroy them.

The Thunderbolts are completely overwhelmed by Sentry’s abilities. However, Sentry eventually turns against de Fontaine, recognizing that she intends to control him. Before he can stop her, Mel activates a kill switch that causes Sentry to collapse. Bob awakens moments later, but something far more terrifying emerges: the Void, a dark manifestation of his trauma and destructive power.

Overwhelmed by the threat, the Thunderbolts initially retreat. Yelena becomes consumed by guilt and believes the team has failed. Alexei reminds her that her value comes from giving others someone they can depend on, just as she once did on her childhood soccer team. When the Void begins consuming New York City in darkness, the Thunderbolts return to save civilians. Yelena deliberately enters the Void to confront Bob and the trauma buried within him.

Inside the Void, Yelena is forced to confront painful memories from her childhood and her struggles with guilt. She eventually finds Bob inside a distorted recreation of his childhood bedroom and realizes that the Void is feeding on his feelings of worthlessness. Yelena encourages Bob to confront the abuse and suffering that shaped him rather than allowing his trauma to control him.

The other Thunderbolts eventually join them. Bob confronts the Void in a manifestation of the laboratory where he was experimented on, but the Void overwhelms him and attempts to consume him completely. Rather than abandoning Bob, the Thunderbolts remind him that he has value and that he does not have to face his pain alone. Their support allows Bob to regain control and reverse the Void’s destruction, restoring New York City.

The Thunderbolts then confront de Fontaine, but she quickly attempts to save herself by manipulating the situation. At a hastily arranged press conference, she claims the group was secretly assembled under her authority to protect the United States and publicly announces them as the “New Avengers.” Although Yelena knows de Fontaine is lying, the team accepts the opportunity to hold her accountable from within the organization.

With Bob temporarily sidelined because of the danger of unleashing the Void, the newly christened New Avengers become public heroes. Alexei enthusiastically attempts to capitalize on their newfound fame, even promoting merchandise featuring the team.

Fourteen months later, the New Avengers face an unexpected legal dispute with Sam Wilson over their use of the Avengers name. As the team debates changing its name, they receive an alarming signal from space. An enormous extra-dimensional spacecraft approaches Earth, bearing a mysterious emblem featuring the number “4”.