Misty, the Gym Leader of the Cerulean City Gym, was first seen fishing on a riverbank near Pallet Town. Thinking she had a big catch, she reeled in Ash Ketchum and Pikachu, who had jumped in the river to escape a flock of wild Spearow. Misty suggested that Ash Ketchum take Pikachu to the nearest Pokémon Center and pointed them in the right direction. In a hurry, Ash Ketchum jumped on Misty's bicycle so that he could quickly get Pikachu to the Pokémon Center. He promised one day to the return bike. Misty eventually follows Ash Ketchum to Viridian City, carrying her bike that was destroyed by Pikachu's Thundershock while battling the flock of Spearow.

Several dislikes have been revealed over time which include carrots, peppers, and most famously bugs. However, Misty has warmed up to a few cuter bug Pokémon which were Ash's Butterfree and Heracross along with Tracey's Scyther. Despite being known as a tomboy she does have girlish tendencies and likes romance along with French things. Misty is also said to have a crush on Ash Ketchum but its largely added in English with a few hints given in Japanese as well along with Rudy, Danny, and Georgio expressing romantic feelings toward Misty at one time or another.

One of her quirks is a tendency to be quick tempered but she also has a compassionate and caring side as shown with Togepi along with others met on her journey with Ash Ketchum. Even with Ash Ketchum and Brock Misty has acted as the voice of reason from time to time and pulled Brock away by the ear to keep him from getting into trouble with a random Nurse Joy, Officer Jenny or anyone else he became infatuated with.

Misty is a very devoted water Pokemon trainer and has a number of achievements including top 8 in the Whirl Cup, winner of the Seaking Catching Contest, and winner of the Celedon City Princess Festival. Despite raising water Pokemon she was afraid of Gyarados after a traumatic experience as a toddler but conquered this fear after taming one at the Cerulean City gym.

She has captured Horsea, Poliwag, and Corsola during her travels with Ash Ketchum along with acquiring Togepi because she was the first living thing it saw after hatching and had imprinted her as its mother and trainer as a result.

The on screen evolutions her team members have gone through were Poliwag into Poliwhirl and later into Politoed after it accidentally grabbed Ash Ketchum's King's Rock and was returned to Misty after being stolen by Team Rocket and released with the rock on its head. Togepi also became Togetic during her brief appearance in Hoenn but was released almost immediately afterward and went to the Mirage Kingdom to protect the other Togepi that live there. The first three team members she is known to have are Staryu, Starmie, and Goldeen, all three acquired prior to her first appearance.

Kasumi the Tambourinist

In PM150, Misty recalled that when she was young she was known as "Kasumi the Tambourinist" (タンバリン使いのカスミ) but her playing skills didn't seem to be too good as Olesia's Wooper closed their ears and it wasn't until Misty's Togepi started playing it that they responded normally to the tambourine. Misty thought she was decent at playing and she couldn't figure out what she was doing wrong.