The book introduces its main character, Leo, at an early age, which is followed by his move from his home state of Pennsylvania to Arizona when he is 12. Before the move, his Uncle Pete gives Leo a porcupine necktie as a farewell present, inspiring him to collect more like it. After his birthday and collection of porcupine neckties are mentioned in a local newspaper when he's 14, Leo receives a second porcupine necktie, left anonymously.
Two years later, Stargirl Caraway arrives at Leo's school, Mica High. Leo learns that up until this point, she has been homeschooled, but even that doesn't seem to excuse her strange behavior; for example, she comes to school in strange outfits—kimono, buckskin, 1920s flapper clothes, and pioneer clothes. She also brings a ukulele to school every day, as well as her pet rat, Cinnamon. She is so different that at first, the student body does not know what to make of her. Hillari Kimble, a well known and somewhat popular girl at Leo's school, declares that Stargirl is a fake, and speculation and rumors abound.
One of Stargirl's quirks is singing happy birthday to students when it is their birthday, bringing her ukulele along to do so. When Hillari orders Stargirl not to sing to her on her birthday, Stargirl sings Hillari's name but directs the song to Leo and mentions in front of everyone that she thinks he is cute. Though at first rejected by most of the students, Stargirl gains a measure of popularity and is asked to join the cheerleading squad after she succeeds in getting the crowd excited about the school's losing football team while cheering for them at a game. Students mimic her behavior, and at lunch, she no longer sits alone. Her antics on the squad spark a boom in audience attendance at sporting events.
However, Stargirl's popularity is short-lived. Thanks in part to her efforts, the football and cheer season is the best in the school's history, and school spirit flourishes; however, students begin to resent Stargirl's habit of cheering for both teams, which before had added to her popularity. Their anger comes to a head during the filming of the student-run television show, Hot Seat, which is run by Leo and his best friend Kevin. During the show, a "jury" of students is invited to ask questions of the guest star. This show's guest is Stargirl, and the session turns into an embarrassing attack on Stargirl's personality and actions. An advising teacher cuts the show short, and it is never aired, but the damage is done. Shortly thereafter, Stargirl stops cheering for both teams at games, but cannot stop herself from comforting a hurt player from the opposing team during a playoff basketball game and is blamed for Mica High's loss in the following game. She is shunned by the entire student body, except for her friend Dori Dilson, Leo, and, to some extent, Kevin.
Leo praises Stargirl for her kindness, bravery, and nonconformity, and the two begin a tentative romance. They spend more and more time together, and Leo experiences her unusual lifestyle and starts helping her with various projects, such as leaving cards for people they don't know and dropping change on the sidewalk for others to find. For a while, he is deliriously happy with their relationship, but as reality sets in, he realizes that the entire school is shunning both of them. In response, Leo convinces Stargirl to act more "normal." She starts going by her real name (Susan), wears typical teen clothing, and becomes obsessed with being accepted and popular. These actions fail to produce results.
Stargirl decides that the best way to become popular is to win the state's public speaking competition, which she does. But when she returns to the school expecting a hero's welcome, only three people show up. Realizing that she has achieved nothing by trying to fit in and has betrayed her true self, Stargirl reverts to her former personality. Seeing that dating Stargirl is getting him shunned by his peer group, Leo parts ways with her so he can be accepted in social company, choosing his peer group as a group over his sweetheart.
Despite the parting, Stargirl attends the school's spring BBQ—the Ocotillo ball—with Dori. Leo watches as Stargirl arrives at the dance on a bike covered in sunflowers. Though initially ignored by the other attendees, something about Stargirl attracts attention and temporary acceptance. She convinces the bandleader to play the "Bunny Hop," and the other students come to join her in the dance until the only people not in line are Hillari Kimble and her boyfriend, Wayne Parr. When the dance ends, Hillari confronts Stargirl, tells her that she always ruins everything, and slaps her as hard as she can. Stargirl returns Hillari's attack with a kind kiss on the cheek. No one in the town sees Stargirl again after that night, and Leo learns that she and her family have moved away to Minnesota.
Flashing forward fifteen years, a now-adult Leo notes that his former high school has become permanently changed, and wonders what has happened to Stargirl. In the end, he reveals that he has received a porcupine necktie in the mail one day before his most recent birthday—presumably from Stargirl.
The story continues with the sequel, Love, Stargirl, which is written from Stargirl’s perspective about her new life after Mica Area High School.
