Thousands of years ago, a unique tribe of Minions, distinct from those that would later serve Gru, embarks on a quest to serve the world's greatest villains. However, they unintentionally end up causing the demise of their masters in a series of unfortunate events. Among them is James, an imaginative Minion with a flair for storytelling and drawing. He quickly forms a strong bond with two companions: Henry, a two-eyed Minion who enthusiastically supports him, and Ed, a mute Minion who uses sign language to communicate, fostering a close friendship within the trio.
Their adventures lead them to serve a variety of masters, one being a Russian warlock who meets his end when a monster, summoned accidentally by Henry from his spell book, wreaks havoc. Ed takes the book along with them as they continue their journey. Later, the Minions chance upon a bank robbery and decide to pursue the robber in hopes of becoming his henchmen. To their surprise, the robber is merely an actor, engaged in filming a chase scene for a 1927 Hollywood movie. Although filmmaker Max is exasperated by the Minions' antics, studio executives Frank and Elwood are enchanted and opt to hire the Minions as stars in his films. This decision catapults the Minions into global fame, as they star in a series of silent films, reveling in a life of Hollywood glamour.
However, with the arrival of sound films, the Minions face a significant challenge due to their incomprehensible language, which leads to immense financial losses for the studio. Consequently, the Minions find themselves out of work. Refusing to give up his passion for storytelling, James devises a plan to create his own film, titled Minions & Monsters, where the Minions confront enormous monsters. This idea is met with resistance from the tribe's leader, Dick, who ultimately chooses to find a new evil master. Unwilling to dismiss James’ vision, Henry and Ed break away to assist him in realizing his film. They present their idea to Max, who encourages James and provides him a film camera to start production.
To bring the movie to life, Ed decides to use the warlock's ancient spell book to summon a squid monster. In a surprising twist, this results in the emergence of a small, green monster named Gary Orkam Oliver Magma Ichabod "Goomi" the Deceiver, who offers to help James discover ideal monsters for his project. Meanwhile, Dort, a man claiming to be an alien robot set on Earth domination, employs the Minions for his mission. During this endeavor, he develops feelings for women's rights activist Debbie and seeks the Minions' aid to win her affection.
Goomi then takes James, Henry, and Ed to a frozen fortress where he liberates sea monsters Howard and Phillip under the guise of casting them for James’ film. However, his true intent is to use them to summon Irene (Eyereen), a colossal, orange, multi-eyed blob monster, with world destruction in mind. Henry learns of Goomi’s sinister plan and attempts to warn James, but Howard and Phillip capture him, persuading James to sacrifice Henry in a scene for the film. As the filming begins, Goomi successfully conjures Irene, unleashing havoc.
In a climactic moment, when Dort and the other Minions spot Irene pursuing Henry through the streets, Dort seems to abandon them at a critical moment, leaving the Minions to confront the chaos alone. Tragically, Irene swallows Henry whole, prompting James to crash a milk car into her in a desperate attempt to rescue his friend. Despite the Minions' best efforts to take down Irene, she continues her rampage. Just when all appears lost, Dort returns alongside the other Minions in spacecrafts, revealing his identity as an alien robot, and together, they manage to eliminate Irene. Henry and James cast an undo spell to send Goomi, Howard, and Phillip back through the spell book. Their heroics earn them public admiration, and Ed captures all the action on film, ultimately allowing the completion of James’ movie.
Months later, Minions & Monsters premieres in theaters, receiving a standing ovation from enthusiastic audiences, while Dort begins a family with Debbie. In a twist, a film museum tour guide named Olivia narrates the adventure of James and Henry, only for it to be revealed that this tour, including the entire plot, is a film within a film directed by James and Henry themselves. In a mid-credits scene, the spell book mistakenly falls into the hands of Gru's Minions, who eagerly test its magic alongside James, Henry, and Gru’s daughter, Agnes.
