As the story begins, Desjardin secretly feels the same disgust everyone at the high school feels for Carrie White. However, when she witnesses Carrie being humiliated by the other girls in the locker room after gym class for her hysterical reaction at her first period, she realizes that Carrie is oblivious to what is happening to her, and feels sorry for her. Desjardin wants to punish the girls who taunted Carrie by having them suspended for three days and banned from the upcoming senior prom, but the principal settles on a lesser punishment: a week of boot-camp style detention in the gym. In Desjardin's view, the only reason the administrators didn't go along with her proposed punishment is that they are all men (unaware that they are all intimidated by Chris' father who is a prominent lawyer), and thus didn't really understand just how nasty the girls' behavior had been. Lead bully Chris Hargensen skips the detention and thus is barred from the prom. The principal reprimands Desjardin for cursing at Chris, but stands by her when Chris' father threatens to sue unless Chris is allowed to attend the prom, unless Desjardin is fired from her job. Meanwhile, Sue Snell, another girl who bullied Carrie, feels remorse for her actions and has her boyfriend, Tommy Ross, take Carrie to the prom to make amends.
At the prom, Desjardin talks with Carrie about her own prom night and later, congratulates her for being voted Prom Queen. As revenge from being banned from prom, Chris has secretly rigged a cord connected to two buckets hidden above the stage where Carrie and Tommy will sit on the thrones. When Chris pulls it both buckets tip over, drenching them with pigs' blood. Desjardin reflexively responds to the prank by laughing. However, she later tries to help Carrie, who pushes her aside with her telekinesis, because she telepathically sees that deep down Miss Desjardin is still laughing at her. Once outside, Carrie uses her gift to wreak havoc on the school with the intention of killing everyone in the gymnasium. She then destroys the entire town on the way home. Desjardin is one of the few survivors of the "Black Prom".
Two weeks after the disaster, and with 440 people dead, Desjardin retires from teaching, saying she is consumed with guilt for not doing more to help Carrie and that she would rather commit suicide than teach again. She also implies in her resignation letter that she feels guilty for having laughed at Carrie instead of helping her.
In the 1976 film version of the novel, Miss Desjardin is renamed Miss Collins, and is portrayed by Betty Buckley. Unlike the character in the book, Miss Collins does not first experience revulsion toward Carrie, as she is suggesting in the beginning that the students pass the ball to Carrie in their volleyball game. After the locker room incident, she also punishes the girls, and when Chris argues with her during detention, Miss Collins slaps her and makes the infuriated Chris skip detention, thus being banned from prom. She becomes more sympathetic and attempts to help Carrie overcome her awkwardness when she realized Tommy asked her to prom, and reprimanded him and Sue for trying to do so.
After Carrie uses her powers to wreak havoc on the school, Miss Collins is seen trying to move the unconscious Tommy, along with another teacher and three students. Carrie pulls her across the floor and pins her against the wall. Carrie then smashes a basketball rafter into her, killing her.