Upon her defeat, the Ultra Wormhole and Nihilego begin to disappear. Encouraging Lusamine to capture the Nihilego that appears in the room so it can be used to crush the player and their friends, Guzma ends up in a battle with Hau while Gladion tries to defeat Nihilego and the player fights Lusamine. A short while later, he rushes to Lusamine's side after she opens the Ultra Wormhole using Nebby's powers, unleashing Ultra Beasts all over Alola. Guzma relents and allows the player to enter Lusamine's mansion after falling once more. Gladion rushes ahead to attempt to defeat Guzma and open the path for the player, but fails, leaving the player to battle Guzma one last time themselves. As the player, Hau and Gladion fight through the Aether Foundation Employees who, along with Faba, are guarding Aether Paradise on Lusamine's orders, they discover a large group of Team Skull Grunts personally led by Guzma guarding the path to Lusamine's mansion, revealing that Lusamine has been secretly controlling Team Skull. At this point, Gladion openly betrays Team Skull and recruits both the player and Hau for a mission to rescue Lillie from where Team Skull took her - Aether Paradise. However, it is subsequently revealed that Team Skull's kidnapping of the Yungoos was a distraction meant to draw the player away from the Aether House so Plumeria could abduct Lillie. He returns the Yungoos after losing to the player again, but vows that he will one day defeat them. After getting past an army of Team Skull Grunts and infiltrating their headquarters, the Shady House, the player comes face-to-face with Guzma, who is holding the Yungoos in his personal quarters. Later on, the player travels to Po Town to retrieve a Yungoos Team Skull stole from a child living at the Aether House. The player wins, and Guzma leaves, saying he'll remember the encounter. When Kukui asks the player to battle Guzma, the boss takes notice of their Z-Ring, and asks why they're taking on the island challenge before immediately dismissing it and accepting Kukui's terms.
To solidify his position, his Grunts have been stealing every piece of Buginium Z across Alola simply to deny its use to other Trainers.
Guzma then criticizes Kukui's idea of building a Pokémon League for Alola while he agrees that some parts of the island challenge are antiquated, he claims there is no need for a League, as he believes he is the strongest Trainer in the region. Guzma first appears in Malie Garden, taunting Professor Kukui and calling both the professor and himself "fellow rejects who never could become captains".