Optimus Prime enters Transformers: The Last Knight as the surviving leader of the Autobots and as one of the central figures remaining from the long conflict between Autobots and Decepticons. Before the events of the film, Cybertron had been devastated and Earth had become increasingly hostile toward Cybertronians. Following the events of Transformers: Age of Extinction, Optimus left Earth and traveled into space in search of the beings responsible for creating the Transformers. His departure left the Autobots without their leader during a period in which Transformers had been declared illegal on Earth and were being hunted by the Transformers Reaction Force. The film therefore begins with Optimus already separated from the Autobots and pursuing a personal objective connected to Cybertron's origins and its creators.

Optimus's arrival at Cybertron becomes the defining event of his history in this film. When he reaches the ruined planet, he immediately recognizes it as his home and reacts to the condition in which he finds it. Quintessa then appears and identifies herself as the "Prime of Life" and claims that she created him. The film presents her claim as part of its explanation for the Transformers' origins, although it does not independently establish every detail of that claim outside Quintessa's own account. She tells Optimus that his war destroyed Cybertron and argues that he must help restore it. Optimus rejects her accusation that he caused the war and identifies Megatron as the one who started it. Quintessa nevertheless takes control of him, tells him that he belongs to her, and makes his restoration of Cybertron dependent upon carrying out her orders.

Under Quintessa's control, Optimus is transformed into the state identified in the film as Nemesis Prime. This is not presented as the discovery of a separate Cybertronian who had previously lived independently under that name. Within The Last Knight, Nemesis Prime is Optimus Prime operating under Quintessa's control. Quintessa explains that her staff, described as her power of creation, was taken from her by her twelve guardian knights and hidden on Earth. She further states that the staff is necessary to restore life to Cybertron. Her plan requires Earth to be sacrificed because she identifies the planet itself as Unicron, an ancient enemy of Cybertron, and intends to drain its life. When Quintessa tells him that Earth will die and Cybertron will be reborn, she explicitly addresses him as "Nemesis Prime." He then states that he will fight anyone who stands in his way.

Nemesis Prime's purpose in the film is therefore directly tied to the restoration of Cybertron. His assigned objective is to recover Merlin's staff from Earth and return it to Quintessa so that its power can be used against Unicron. His role is consequently a temporary extension of Quintessa's plan rather than a new life history separate from Optimus Prime's. The film does not give Nemesis Prime an independent childhood, separate origin, separate military career, separate relationships, or a life existing before Quintessa takes control of Optimus. Those details would go beyond what the movie establishes.

The conflict at Stonehenge becomes the decisive point in Nemesis Prime's brief existence. Optimus reaches Earth and confronts Cade Yeager, Bumblebee, and the others while attempting to obtain the staff. During the confrontation, he fights against people and Cybertronians who were previously connected to him. The control imposed upon him is eventually disrupted when Bumblebee's voice triggers Optimus's memories and identity. The film treats this moment as the restoration of Optimus Prime rather than the death of a separate character named Nemesis Prime. After that point, he is again operating as Optimus and takes part in the effort to prevent Quintessa from destroying Earth.

Once free of Quintessa's control, Optimus resumes his role in the final battle and helps stop the immediate threat to Earth and Cybertron. He confronts Quintessa's forces, participates in the assault on the enemy's position, and helps prevent the destruction of Earth. His actions during this portion of the film restore him to the position he occupied before his corruption. The film does not establish that the Nemesis Prime identity permanently changes his name, status, or existence. Instead, the conclusion shows Optimus continuing as the same individual after the control has been broken.

By the end of The Last Knight, Optimus's historical position has changed from that of an isolated Cybertronian leader searching for his creators to a figure once again directing the Autobots toward their homeworld. His closing message states that Earth and Cybertron are now connected and that the two worlds must repair their planets and work together to survive. He then broadcasts a call to the Autobots telling them that it is time to come home. The film consequently ends with Cybertron's restoration becoming the next stage of his life rather than the conclusion of his story.

Taken strictly from the movie, Optimus Prime's biography in The Last Knight is therefore the continuation of a long life shaped by the destruction of Cybertron, his role as the Autobot leader, his departure from Earth to seek his creators, his encounter with Quintessa on the dying remains of Cybertron, his forced transformation into Nemesis Prime, his ordered mission to retrieve Merlin's staff, his temporary use as an instrument of Quintessa's plan, his recovery of his true identity through Bumblebee's voice, and his return to the Autobot cause. The film leaves his deeper origins deliberately tied to the mystery of the Transformers' creators and Quintessa's claims, while his immediate legacy is left in the decision to bring the Autobots back toward Cybertron and work toward the survival and repair of both worlds.