Kanto
Before James ran away from home when he was a child, Growlie was his only friend on his parents' estate. The two were inseparable, and Growlie comforted James when he faced problems with his parents and arranged fiancé, Jessiebelle. When the stresses of home became too much, James ran away from home, leaving Growlie behind at the mansion, possibly at his request. Growlie lives in an extravagant doghouse, which was so large that Ash and his friends mistook it for being the family's actual mansion. Misty even commented, to her later embarrassment, that it was the largest mansion she'd ever seen.
Years later, in Holy Matrimony!, James returned to his parents' home after hearing that they had died. However this turned out to be a hoax for them to get him to marry Jessiebelle, and after the deception was revealed, Jessiebelle trapped James in the family's dungeon. Ash, his friends, Jessie and Meowth, let Growlie out of his doghouse and it burst into the dungeon, rescuing its long-lost master. The two were thrilled that they'd been reunited, unfortunately the happy moment had to be cut short when Jessiebelle and her Vileplume located and attacked the two. After defeating the Vileplume and temporarily chasing Jessiebelle off the estate, James once again left home, set on giving up on his inheritance and continuing to live with Jessie and Meowth. He told Growlie to stay behind to watch after his parents. Saddened, Growlie howled as James walked away from the mansion.
Sinnoh
Growlie made its reappearance in The Treasure Is All Mine!, where it accidentally blew Team Rocket's cover when they were infiltrating one of James's family's vacation homes because it was so happy to see James again. Growlie proceeded to help James until he was able to once again evade his ever-pursuing family. Though they rarely see each other anymore, Growlie remains protective and devoted to its master.