Speak tells the story of Melinda Sordino, a ninth grader at Merryweather High School in Syracuse, New York. August before her freshman year, Melinda and her closest friends attend a party with seniors and beer. At the party, Melinda feels uncomfortable and out of place. She gulps down a couple beers before walking outside for some fresh air. While outside, Melinda meets Andy Evans, an attractive senior boy. Andy begins dancing with and kissing Melinda, and Melinda is taken aback but too drunk to say anything. Andy pushes her to the ground and rapes her. In her confusion afterward, Melinda dials 911 and the police arrive at the party, but Melinda finds herself unable to tell anyone what happened. When the entire school discovers that Melinda broke up the party and got some students arrested, her friends stop speaking to her. No one knows that she was raped.
She arrives friendless on her first day of ninth grade and receives angry glares from strangers. She decides that speaking only hurts her, and remains mostly silent. Melinda slips into depression and her grades suffer. She finds an abandoned janitor's closet and makes it her sanctuary.
Initially, Melinda is befriended by Heather, a new girl from Ohio. However, Heather is eager to be a part of the social scene and she soon joins a clan known as "the Marthas." Heather realizes that having Melinda as a friend hurts her social reputation, and she tells Melinda that they can no longer spend time together. As Melinda sinks deeper into depression, she begins to skip class. Her parents and teachers notice, but believe that it is just an immature attention-seeking ploy. Only her art teacher, Mr. Freeman, observes Melinda's depressed behavior. He encourages her to use her voice and shows interest in her artwork. Melinda also befriends her lab partner, David Petrakis. Like Mr. Freeman, David pushes Melinda to speak up.
Over the course of the school year, the story of Melinda's past unfolds. She begins to admit to herself what happened and gradually stops running away from the memory of it. She still, however, remains silent. In the spring, her former best friend, Rachel, begins to date Andy Evans. Horrified by this, Melinda knows that she must warn Rachel about the danger of spending time with Andy. Melinda opens up to Rachel about the rape by exchanging notes with her in the library. Rachel is receptive until Melinda names Andy the perpetrator, at which point she angrily leaves the room. However, Rachel does, in fact, listen to Melinda's story. The next weekend, she publicly leaves and humiliates Andy at the prom.
The following week, Melinda decides she is ready to move out of her janitor's closet. She no longer feels like hiding. While cleaning it out, however, Andy enters and locks her in the room with him. Angry that she talked to Rachel, Andy attempts to rape Melinda a second time. This time, however, Melinda screams and fights back. The lacrosse team hears Melinda's cries and rescues her from Andy. By the next day, everyone knows Andy and Melinda's history. Melinda's popularity skyrockets.
In the last chapter of the novel, Melinda sits in Mr. Freeman's room on the final day of school finishing up her yearlong art project. After she turns it in, Mr. Freeman gives her an A+. He says that he knows she has been through a lot. Prompted by this statement, Melinda decides to tell Mr. Freeman her entire story. The Melinda we see at the end of the novel is not the same Melinda that arrived friendless on her first day of ninth grade. This Melinda is ready to accept what happened and is prepared to seek help. This Melinda speaks.