Jack lives with his Ma in Room, a secured single-room outbuilding containing a small kitchen, a bathtub, a wardrobe, a bed, and a TV set. Since it is all he has ever known, Jack believes that only Room and the things it contains (including himself and Ma) are "real." Ma, unwilling to disappoint Jack with a life she cannot give him, allows Jack to believe that the rest of the world exists only on television. Ma tries her best to keep Jack healthy and happy via both physical and mental exercises, keeping a healthy diet, limiting TV-watching time, and strict body and oral hygiene. The only other person Jack has ever seen is Old Nick, who visits Room at night while Jack sleeps hidden in a wardrobe. Old Nick brings them food and necessities. Jack is unaware that Old Nick kidnapped Ma when she was nineteen years old and has kept her imprisoned in Room for the past seven years; Jack is the product of Old Nick's rape of Ma.
A week after Jack's fifth birthday, Ma learns Old Nick has been unemployed for the past six months and is in danger of losing his home to foreclosure. Feeling certain that Old Nick would kill them both before letting them free, Ma comes up with a plan to get Jack out of Room by convincing Old Nick that Jack is deathly ill. Jack is confused by the concept of leaving Room and interacting with other people, but Ma eventually convinces him to help her. When Old Nick refuses to take Jack to a hospital, Ma then pretends that Jack has died. Old Nick removes Jack, wrapped in a rug, from Room. Jack escapes Old Nick and manages to reach a friendly stranger, who contacts the police. In spite of his fear, confusion, and inability to communicate effectively, Jack directs the police to Room to free Ma.
The two are taken to a mental hospital, where they receive medical evaluations and a temporary home. Old Nick is found and faces numerous charges of abduction, rape, and child endangerment that will likely lead to twenty-five years to life in jail. While in the hospital, Ma is reunited with her family and begins to relearn how to interact with the larger world, while Jack, overwhelmed by new experiences and people, only wants to return to the safety of Room. Meanwhile, the case has attracted much attention from the public and the mass media, making it even harder for Jack and his mother to start leading a normal life. After a television interview that ends badly, Ma suffers a mental breakdown and attempts suicide. Jack goes to live with his grandmother and her new partner for several days. During this time Jack becomes even more confused by his surroundings, including his new extended family.
After Ma recovers, she and Jack move into an independent living residence, where he and Ma begin making plans for their futures. Jack becomes more conflicted and frightened by his mother's growing independence and his desire to keep her for himself. At the same time, Jack himself is growing and changing as his world expands. Finally, Jack requests to visit Room. He and Ma return to the scene of their captivity, but Jack no longer feels any emotional attachment toward it and is able to say his goodbyes before he and Ma leave Room for the final time.