Jessie's Frillish first appeared in BW109, debuting along with James's Amoonguss when Team Rocket attacked Ash and his friends for the first time since their "Operation Tempest" and temporary retreat back to Kanto.
When Ash and friends were helping the rookie Trainer Nonomi to gain some experience, Team Rocket surprised them, sent out their new Pokémon, and used a combination of Mist and Stun Spore on them and their Pokémon, reducing the visibility to almost nothing and paralyzing Iris's Emolga and Cilan's Stunfisk at the same time, thus leaving Ash alone to face Team Rocket with Pikachu. After Amoonguss had successfully knocked Pikachu out, Jessie had Frillish to use Psychic, lifting Pikachu into the air and towards Team Rocket's mecha. However, thanks to the distraction provided by Nonomi and her Tepig, Pikachu was freed, although Tepig got caught in the process. For a getaway distraction, Team Rocket fired a combination of BubbleBeam and Hidden Power, which, much to their surprise, was endured by Ash's Unfezant, followed by an Air Cutter and an Aerial Ace to defeat Frillish and Amoonguss, respectively.