At Porta Vista, Brock, Ash, and Misty were trying to return to the mainland when Misty noticed an injured Horsea near the coast. The little seahorse squirted out a warning in ink that the children didn't understand.
Later, the kids learned that a woman named Nastina was trying to build an underwater resort in the local reefs, and that her workers were being attacked by many Tentacool. A strange chain of events lead to the community being attacked by a gigantic Tentacruel, who was angry at the humans demolishing the reef. Horsea and Misty's pleading saved the city, and Horsea then joined Misty's team.
Much later, near the end of the Kanto adventures, Horsea was feeling ill because Misty wasn't letting him out enough to get any exercise. With no ocean nearby, Misty decided to take him home to Cerulean City, where he could play and swim in her Gym's many aquariums. After participating in a water ballet, Misty left Horsea and her Starmie in the care of her sisters.
Later, Misty reclaimed Horsea and Starmie when her travels in Johto were finished and she became Cerulean's Gym Leader.
Horsea, like Goldeen, has trouble functioning on land, so she didn't use him much in her adventures. However, when he was used, he tended to be very resourceful - using ink to draw pictures or leave trails.
In the Special episodes, Horsea is seen saving Misty from the whirlpool her Gyarados had created. It was also seen being fed Pokémon food by Misty.