In season one, Zoey Brooks (Jamie Lynn Spears) and her younger brother Dustin (Paul Butcher) arrive at Pacific Coast Academy (PCA), a school which recently went Mixed after being a boys' school since its founding. Zoey meets her first friend Chase Matthews (Sean Flynn), who, after meeting her, realizes that he has a crush on her. Zoey then meets her roommates, fashionable tomboy Dana Cruz (Kristin Herrera) who is also great at basketball,and boy-obsessed Nicole Bristow (Alexa Nikolas). She also meets aspiring scientist/inventor Quinn Pensky (Erin Sanders) who is very quirky and does weird science experiments in her room, humorous Michael Barret (Christopher Massey) who is one of Chase's roommates and best friend since the 6th grade, and rich, spoiled and obnoxious Logan Reese (Matthew Underwood) who is Chase's other roommate and tries to make out with every girl he can. With Chase's help, she gets Quinn a boyfriend named Mark Del Figgalo (Jack Salvatore Jr.) After destroying his last relationship on accident not knowing he already has a girlfriend.
Season two follows Zoey's second year at PCA. Dana has been accepted by a European student exchange program and is now studying in Paris, much to Nicole's delight. Zoey and Nicole get a new roommate, aspiring actress Lola Martinez (Victoria Justice). At first, Lola tricks them into thinking she is a goth voodoo punk freak and they try to find a way for her to leave. However, they catch Lola talking on the phone to her friend telling her how well her little scheme has worked — she's been caught. Zoey and Nicole confront her and she admits to it and confesses that it was an acting exercise. Zoey and Nicole forgive her and they are henceforth best friends. Their affection can also be seen in the next two seasons.
In season three, Zoey and the rest of the gang return to PCA. Nicole has left PCA because she was diagnosed with Obsessive Male Gender Disorder (OMGD), and is sent to an all-girls school. This causes Zoey and Lola—much to their dismay—to become roommates with Quinn, after she's accidentally assigned to a dorm that doesn't exist by Coco, their dorm advisor, who they also help get back together with Carl, her on and off again boyfriend. At the end of the season, in the "Goodbye, Zoey?" TV film, Zoey transfers to Covington (a new boarding school) in England After she tries to talk to Chase about it but he earlier heard about it and thought that she had already made up her mind on moving. Due to a webcam malfunction, Zoey finds out that Chase loves her and has loved her since the day they met.
In season four, the final season, Zoey returns to PCA, only to find that Chase transferred to Covington in England believing Zoey was still enrolled there. Zoey and Chase reveal their love for each other and want to be together, but Chase has to stay a full semester at Covington. When they finally have their first date over web chat, it doesn't go well, so they decide to put off their relationship until Chase's return. Meanwhile, Logan and Michael get a new roommate named James Garrett (Austin Butler), who eventually becomes Zoey's boyfriend because someone starts a rumor that they are dating, but eventually end up liking each other. Quinn and Logan begin to date, but they hide their relationship from their friends because they are embarrassed that they are dating each other. In the series finale, entitled "Chasing Zoey", the kids get ready for prom. Zoey and James end their relationship, and Chase surprises Zoey once he returns home to PCA. They finally have their long awaited first kiss and begin to date. The last episode aired on May 2, 2008.