Optimus Prime commands the Autobot forces. Following altered events from Transformers: Prime's second season in the Japanese continuity, where the Autobot base's destruction was prevented, the Autobots and Decepticons united against a new threat: the Predacons, created by Shockwave but later rebelling. To combat the Predacon menace across the universe, Optimus Prime and his forces adopted upgraded "Hunter Mode" armor, called "Preda-Armor," developed by Ratchet. Tracking a group of Predacons led by the Demon Emperor Dragotron to Earth, Optimus Prime participated in a decisive battle that resulted in Dragotron's defeat. Dragotron was sealed beneath Mount Fuji using the power of one of five mystical Legendiscs. With Dragotron imprisoned, Optimus Prime entrusted Earth's protection to two specialized three-member Autobot combiner teams, the Samurai Team and the Shinobi Team, known as Swordbots, before departing with the main Autobot forces to confront the remaining Predacon threat across the cosmos.

When activity at Mount Fuji caused Dragotron's partial awakening and the rise of his Four Oni generals—Budora, Gaidora, Bakudora, and Judora—Optimus Prime remotely coordinated the response from space. He contacted the awakened Samurai and Shinobi Swordbot teams, partnered with human allies Isami Tatewaki and Tobio Fūma respectively, tasking them with locating and securing the remaining Legendiscs before the Predacons could acquire them. These artifacts were scattered across historical time periods on Earth, accessible via "Time Slip" abilities activated at specific points. Optimus Prime provided strategic guidance, emphasizing the critical need to prevent the Predacons from obtaining the Legendiscs, as their combined power could fully revive Dragotron.

Later in the conflict, Optimus Prime returned to Earth in an upgraded form, "Optimus ExPrime." This form featured enhanced capabilities, including triple-changing between robot, bullet train, and dragon alternate modes. The dragon mode, designated "Guren Dragon," provided significant aerial combat prowess. Optimus ExPrime also gained the ability to combine with other Autobots. He performed a "Renketsu Sanjō Gattai" (Linked Triple Combination) with the Samurai Team to form "DaiKenzan," and later combined with the Shinobi Team to form "DaiGekisou." These combined forms were deployed during critical battles against the Predacons, particularly the final confrontations to thwart Dragotron's resurrection and the Four Oni's plans.

Throughout the conflict, Optimus Prime maintained his role as leader. He prioritized protecting Earth and its human inhabitants, entrusting specific missions to the Swordbot teams and their human partners while providing oversight and reinforcements when necessary. His actions focused on preventing the Predacons from harnessing the Legendiscs' power and ensuring the safety of sentient beings.