Professor Sycamore made his first appearance in Lumiose City Pursuit!, when Ash, Clemont and Bonnie brought an injured Froakie to him. Sycamore treated Froakie while explaining that he used to be owned by Trainers but had severe behavioral problems which caused him to either abandon or be abandoned by his past Trainers. Sycamore also explained that his area of research was Mega Evolution, and Garchomp was the Pokémon he was researching since she was capable of achieving it.
After Team Rocket's failed attempt to steal Froakie caused Garchomp to go wild, Professor Sycamore joined Ash in his attempt to calm her down but was forced to simply watch from the bottom of Prism Tower. After the situation had been resolved, he thanked Ash by giving him a new Kalos Pokédex and allowing him to take Froakie, who had bonded with the Trainer, with him.
In A Battle of Aerial Mobility!, Sycamore met Serena as she arrived to pick her starter Pokémon.
He appeared again in Mega-Mega Meowth Madness!, where he met up with Ash, Serena, Clemont, and Bonnie when they returned to Lumiose City. Later, he was captured by Team Rocket, who sought for his knowledge about Mega Evolution. Serena and Bonnie were also captured when they tried to help the Professor. The three were rescued by Ash, Pikachu, Clemont, and a Chespin from Sycamore's lab, but Team Rocket activated their newest mecha, which chased them across a forest. After Ash and Clemont unsuccessfully tried to defeat the mecha with Pikachu and Chespin, the group was saved by Blaziken Mask and his Blaziken, who destroyed the mecha, and Team Rocket was then sent blasting off by Ash and Clemont. At the end of the episode, Sycamore allowed Clemont to capture Chespin when it wanted to travel with the group.
He appeared in Mega Evolution Special I in a flashback to Alain's past working for him as an aide.
In The Bonds of Evolution!, he appeared to meet with Diantha regarding Mega Evolution. He attempted to charm her secretary, Kathi Lee, when she interrupted, only to be hit with a book. Later, he filmed Ash's battle with Diantha and Gardevoir Mega Evolving against Team Rocket.
Professor Sycamore appeared again in Summer of Discovery!, where it was revealed that he invited Ash and company to participate in his annual Pokémon Summer Camp. It was also revealed he was the one who gave Tierno, Shauna, and Trevor their starter Pokémon. He, along with his assistants, appeared throughout the event to officiate activities and announce winners.
He appeared in flashbacks in Mega Evolution Special II and A Showcase Debut!.
He reappeared in Mega Evolution Special III, where he saw a TV report that showed Alain fighting Primal Groudon, Primal Kyogre, and Mega Rayquaza and was shocked to see him there.
He reappeared in Garchomp's Mega Bond! where he Mega Evolved his Garchomp for the first time.
He appeared again in Performing with Fiery Charm! where he watched Serena competing in the Dendemille Town Pokémon Showcase along with his lab assistants Sophie and Cosette.
He reappeared in Cloudy Fate, Bright Future! and All Eyes on the Future!.