The show was set in Philadelphia, PA. It started telling the story of 11 year-old Cory Matthews, played by Ben Savage, who desperately wanted to make sense of the world around him. He found his best friend in Shawn Hunter, played by Rider Strong, also 11 years old, who lived in a trailer camp with his very aggressive parents. Cory had it way better though, since he lived in a nice home with his father Alan, played by William Russ, his mother Amy, played by Betsy Randle, and his brother and sister, Eric and Morgan, played by Will Friedle and Lily Nicksay (Morgan was later played by Lindsay Ridgeway).

In school, Cory was constantly terrorized by his teacher George Feeny, played by William Daniels, who unfortunately also lived next door from him. Cory developed a serious crush on one of his classmates, Topanga Lawrence, played by Danielle Fishel. As the series progressed the feelings between the two turned into true love and they had a very cute relationship that later even turned into marriage.

When Cory entered high school and thought he had finally gotten rid of Mr. Feeny, he realized much to his horror that Mr. Feeny was now the principal at John Adams High School. He faced many demons in this new phase, including a new bully Harly Kiner, but high school also came with good things. Shawn and Topanga were also there, and he met new people like Joey and Frankie, and also a very cool new teacher Mr. Jonathan Turner, played by Anthony Tyler Quinn, who later became Shawn's legal guardian.

Later they all attended Penbrook College, where Cory's brother Eric was already going. We got to know Jack Newman, played by Matthew Lawrence, who was Eric's roommate, and who later turned out to be Shawn's half brother. Shawn met Angela Moore, who later became his girlfriend. Mr. Feeny also found love in Ms. Bolander who was the Dean of Admissions at Penbrook College.

In the last season, Cory and Topanga finally got married and relocated to New York with Shawn and Eric to start a new life.