Much like the original show, 90210 follows the move of a family (parents Debbie and Harry Wilson, their daughter Annie and adoptive son Dixon). This time however, Harry is actually from Beverly Hills and comes back both to look after his mother Tabitha and to work as the principal at West Beverly Hills High School. All of them struggle to adjust to their new lives: Annie has a hard time balancing romances (starting with rich kid Ty) and friendships as well as popularity and identity; Dixon has issues with his adoption and African-American heritage; Harry and Debbie struggle with the revelation that Harry has a son with Tracy Clark, his former high school sweetheart.

Tracy Clark has a daughter of her own, Naomi Clark, who dates jock Ethan Ward, brief rival of Dixon, with whom she soon breaks up and who gets back with Annie with whom he had a fling years prior. Both girls alternate between enemies in a love triangle and almost sisters due to their parents' child. Their respective mothers find in a love triangle of their own after Tracy's marriage to Charles Clark implodes (which Naomi takes quite badly) and she appears to want Harry back. Naomi's fight with Annie forces her out of the crowd after she uses Annie's ex-boyfriend Jason as a weapon to get back at her for hiding her relationship with Ethan. She becomes friends with older girls and starts flirting with Ozzie, a rather alternative student.

Sean Cavanaugh arrives in Beverly Hills as the purported biological son of Harry and Tracy, and is introduced as an Army soldier in between tours of duty in Iraq. The Wilsons struggle to accept Sean into the family, especially when Harry tries to regain the years lost with the man he believes is his son. Tracy and Naomi, on the other hand, are far more accepting of Sean. Sean is eventually revealed to be a con artist when Annie and Debbie convince Harry to demand Sean take a paternity test before giving him $200,000 that he allegedly needed to cover gambling debts owed by his adoptive father. He leaves town without a trace, but not before swindling Tracy out of the money. Further widening the rift between them, Naomi blames Annie for Sean's heist, as Tracy was forced to make concessions in her divorce to raise the money. After Sean's heist was revealed, Naomi came home to find her father, saying that Tracy had gone to New York "to think it out", and that she was to live with him and his girlfriend Gail. However, Naomi returns to her old home one day to overhear her father having yet another affair, this time with his real estate agent. Naomi uses this information as blackmail to move out of her father's home and into a hotel room.

Naomi's best friend, fallen starlet Adrianna Duncan battles a drug addiction. This gets her into trouble when Harry decides to clean the school, thanks to the help of a cop, Kimberly McIntyre, under cover as a student. Kimberly begins a relationship with teacher/lacrosse coach Ryan Matthews, which gets him into trouble with the school. Guilt-ridden, Kimberly does her best to solve the case, giving Ryan his job back, although he takes a leave of absence to rethink his life, and Adrianna lands in rehab, after almost getting Naomi in legal troubles as she took the blame for the drugs. There she begins a relationship with Navid Shirazi, head of the school's paper and Dixon's best friend, who paid for her rehab. Although at first she only does it to "repay" him, they start to genuinely care about each other. Adrianna later discovers she is pregnant as a result of her promiscuity while she was addicted. After telling Navid of her pregnancy, he breaks up with her. Adrianna, after almost getting into a car crash, makes a doctor's appointment, where it is revealed that she's too far along for abortion to be an option. It is later revealed that the father of Adrianna's child is Ty, although it is unclear when they slept together.

Also featured is Silver, Kelly Taylor's half sister and Naomi's former best friend until the later revealed Silver's father's affair. She quickly befriends Annie and starts dating Dixon, who is somewhat taken aback by her not-so-90210 lifestyle, as she is a virgin who doesn't care about popularity. Dixon tells Silver that he loves her, which causes them to get in a huge fight over her not saying it back. Being upset over the fight and Silver's intense mood swings, Dixon breaks up with Silver at a cast party. Kelly herself has become guidance counselor at West Beverly and has a son named Sammy. She briefly dates Ryan before leaving to work on her relationship with long-time love Dylan McKay - Sammy's father - which briefly causes friction with Brenda Walsh as both struggle with their lingering feelings towards Dylan. When Kelly returns, she not only discovers Ryan's relationship with student/cop Kimberly but also that he slept with Brenda, again recreating the rift between the two friends. Following Brenda's discovery that she cannot have children, however, the women are drawn together in an accord once again.