The novel is split into five chapters.
The novel opens with Jack turning five and Ma giving him a drawing she did of him as a gift. The narrative perspective is Jack's; therefore, the dialogue is extremely matter-of-fact and juvenile. He describes his interactions and daily routines with inanimate objects, such as the table and the spoon. Jack and Ma sing some songs together. Ma takes two painkillers for her bad tooth. Jack watches TV and interacts with Dora the Explorer as if she were real. Ma measures Jack’s height on the door frame. They complete more of their daily routine, such as reading more books and doing exercises. They have a nap, and then they have dinner. Ma and Jack make a birthday cake, but Jack throws a tantrum because there aren’t five candles. He shouts that she should have asked for candles as a Sunday treat. Ma writes a shopping list and leaves it. Jack goes into the cupboard to sleep while Old Nick, the man whom the reader learns captured Ma and imprisoned her in Room, visits Ma in the night.
Jack describes how he ‘has some’, referring to breast milk from Ma. The next day, their routine continues. They make a ball out of scrunched-up paper and play with it. While Ma naps, Jack finds a mouse and lures it out with crumbs. Ma tries to kill it, and Jack is distressed. After dinner, they watch TV and try to imitate the presenters to increase their vocabulary. Old Nick visits and has some birthday cake, telling Ma he would have bought Jack a present if he had known. Jack counts the creaks of the bed—what the reader understands to be the sound of Old Nick raping Ma—until they stop.
Jack cries the next day, as he hopes Old Nick will bring him a dog. After lunch and a nap, they do their routine of screaming at the skylight, in hopes that someone will hear them. When Jack wakes up the next day, Old Nick has bought him a remote-controlled Jeep. Ma cleans Room, and Jack plays with the Jeep all day. When Old Nick visits, Jack can hear him talking about how the groceries were a ridiculous price. Jack counts the creaks again. Jack still has the remote in the cupboard; he makes the Jeep fall off the shelf, and it hits Old Nick. Old Nick gets angry and leaves.
The next morning, Jack sees dirty marks around Ma’s neck from where Old Nick forcibly grabbed her. They begin to play their usual games; Scream goes on for longer than usual. Jack sees an advertisement for Ma’s painkillers on TV and thinks that those images are the same thing as her real painkillers. Ma tries to explain to Jack how the TV shows images of real things. Jack can’t stop thinking about the things "Outside." The next day, Ma is "gone," in a comatose state; this happens occasionally and Jack is used to it, though it profoundly discomfits him.
Jack watches TV all day, finding raw food when he is hungry. He examines the marks on Ma’s neck and wants to hurt Old Nick. He contemplates the TV, what is real, and what is not. In the night, Jack is woken up by Ma flashing the light on and off. The next day is Saturday; they play some more games, and Jack hears more stories. When Old Nick visits, Ma asks if they could have an extractor fan installed. He gets increasingly annoyed, telling her she is privileged in Room compared to some people.
The next morning is Sunday, and they have bagels for breakfast. Ma’s rotten tooth comes out and Jack decides to keep it. The narrative begins to focus more on Old Nick’s nightly visits. Ma asks for vitamins to keep them healthy. He tells her that he has been jobless for six months now. During the night, Jack gets out of bed to look at Old Nick. He wakes up, and Ma attacks him for trying to go near her son.
To punish Ma for her outburst, Old Nick cuts the power and stops bringing them food. Ma begins to realize that Old Nick would rather kill them then let the police discover his secret.
Ma finally begins to tell Jack her story for the first time. Jack stands on some chairs to see out the skylight, then Ma tries to explain the concepts of what is real and what is in the outside world. Jack has a hard time understanding this and thinks that Ma is lying.
The next day, it is colder. Jack sees an airplane through the skylight and begins to believe Ma’s explanation a little bit. Ma tells Jack that Old Nick abducted her when she was 19 and has kept her imprisoned all these years.
Eventually, after three utterly miserable days, the electricity comes back on.
The next day, Plant is dead due to the cold. Jack asks if there is water in the outside world, and Ma tells him about lakes and rivers. When Old Nick abducted her, he used the excuse that his dog was missing. Jack asks if the dog is sick, and that gives Ma an idea: if she were to pretend that Jack was sick, then Old Nick would take him to a hospital on the outside. Jack hates the idea of being separated from Ma and refuses to do it. That night, Ma shows Jack the full moon. Jack eventually, reluctantly, agrees to her plan. They discuss how Jack is supposed to behave over and over again.
The next day, Ma makes the room smell like diarrhea and smears her own sick on Jack, after making him hot with a flannel. When Old Nick visits, he refuses to take Jack to a hospital, but he says that he will go get some drugs.
Ma turns to Plan B, which she was prepared for and was actually hoping for: Jack will pretend to be dead, Ma will roll him up in a rug, and Old Nick will take him outside to bury him. Jack will unroll from the rug and escape. They spend the whole day practicing rolling him up and escaping. Jack takes Ma’s old tooth in his sock to bring a piece of her with him. Ma also gives him a note for when he is found.
In the evening, Old Nick comes to the room and Ma puts on a performance of tears and grief. Old Nick agrees to remove Jack and bury him somewhere away from his property. He puts Jack in the bed of his truck and drives away. At a stop sign, Jack manages to wriggle free, but he screams and Old Nick hears him. Jack runs away from the truck into the woods, but Old Nick catches him. A man walking his dog sees them and, finding the situation odd, calls the police. Old Nick runs away, leaving Jack.
The police arrive. Officer Oh puts Jack in the patrol car. She patiently tries to decipher where Ma is being kept, and she manages to narrow it down to an outside structure with a skylight. They find Ma, and she comes running out to Jack. He asks if they can go back to bed in Room.
The police take Ma and Jack to a psychiatric hospital so they can recover in private. Jack doesn’t understand why Ma throws away his underwear, and he also does not understand all the lights of the hospital. They meet Dr. Clay, who will oversee their care. They have to wear masks to keep all the germs of the outside world out. Jack struggles to adjust to life outside of Room, with everyday activities such as a shower proving to be a challenge. A nurse, Noreen, looks after them, helping them down to breakfast and giving Jack an Easter egg.
Dr. Clay takes Jack for some testing; Jack screams when he has to have blood samples taken. The doctor explains to Ma that Jack is infant-level in his mannerisms and that he was so used to a confined space that he cannot gauge distance properly. Noreen brings them new clothes, and Jack finds it strange that Ma is dressed in skinny jeans. Ma’s mother visits them, and Jack gets to meet his grandmother. They talk about Ma’s abduction and how, at the time, the police had concluded that Ma had run off. Ma finds out that her parents divorced and that her mother has a new partner, Leo. Jack finds it strange that you can eat syrup with pancakes and that cleaners wash the sheets for them.
Ma urges Jack to go outside, but he is reluctant and has a panic attack when they get outside. The pair open their fan mail, and Jack has received many toys for his bravery; Ma says he can keep five, but he keeps six. Ma talks to Noreen about the charges that will be brought against Old Nick; we learn that Ma was pregnant once before, but the umbilical cord was wrapped around the baby’s neck and she had a stillbirth. Ma persuades Jack to go outside, and Noreen suggests that he pretend that they were reading about themselves in a book, in order to cope.
Ma is reunited with her brother, Paul, and his partner, Deana. Paul says that Jack can meet his cousin, Bronwyn, soon. Jack meets Leo properly and labels him “Steppa” for "step-grandfather." Jack continues to ask if the days of the week are the same as in Room, and he wonders what they’ll request for the Sunday Treat. They go on an outing to the dentist to begin fixing Ma’s teeth.
When they come back from the clinic, Ma’s dad has flown from Canberra to see them. When he sees Jack, he is repulsed and cannot stop thinking of him as the result of rape. Ma screams at him, and he leaves. Ma agrees to do a television interview so that the money can go towards Jack’s college fund.
Jack screams when Ma tries to leave, and he is allowed to sit by the side of the interview. The interviewer is a patronizing lady; she comments on the stillbirth when asked not to, and she is shocked when Ma reveals she still breastfeeds Jack. Ma cries, and Jack runs to her side.
The next day, Ma is "gone." Paul was supposed to take them both to see the dinosaurs at the Natural History Museum, and Jack decides to be brave and go anyway. On the way to the museum, Paul and Deana need to pop into a mall to get a birthday present for Bronwyn’s friend’s party later in the day. They buy Jack a Dora the Explorer backpack, but he gets in trouble when he tries to put a copy of one of his favorite books from Room, Dylan the Digger, in it, unaware that this is stealing. Deana takes Jack and Bronwyn to the bathroom; Jack touches Bronwyn inappropriately—out of curiosity—and Deana hits his hand away. They drive back to the clinic. When they get back, Jack finds Ma unconscious from an overdose of painkillers.
Jack goes to live with his Grandma while Ma recovers from her suicide attempt. He asks if she is only pretending to be dead, and Grandma is obviously worried. Jack sleeps on a blow-up bed in Grandma and Leo’s room. Ma’s condition is stable, and Grandma decides that Jack cannot spend all day in front of the TV again. Grandma takes Jack to a play park, but she gets angry when he cannot interact properly with other kids. She forgot to put his sunscreen on, so Jack is burnt.
Jack asks when Grandma and Steppa will die. He sees a bee and gets stung when he tries to stroke it. In the kitchen, Jack discovers matches and lights one. Steppa stamps it out and helps him to learn about the different kitchen implements, like the grater. Doctor Clay visits Jack and lectures Grandma about looking after Jack properly. Grandma takes Jack to another play park, but he gets shy in front of another child and they go home.
At home, Jack can hear Grandma and her friends talking about him. They call Grandma "heroic" for looking after him. The next day, Grandma has to have a bath with Jack, and then they cut his hair. Jack checks he still has his strength, like Samson after his haircut.
Grandma and Jack go on an outing. They go to the post office and send Ma a picture of a rocket. They visit Paul at his office. Then, Grandma buys Jack some yellow Crocs. When Jack plays with a little boy, Walker, he tries to give him a hug and accidentally hurts him. Jack says that he loves him.
Jack continues life at Grandma’s, talking to Ma on the phone. They go to the store to buy Jack a football. A woman recognizes Jack, and people begin getting lots of autographs of him; when Grandma notices, she is furious and yanks him home.
Jack is painting in Grandma’s kitchen when Ma appears. They have dinner there, and Ma announces they’ll move to an independent resident facility. They move in, and Jack gets his own room for the first time. Ma and Jack write down everything that is new to them and everything that they want to try.
Jack asks Ma to take him back to Room to visit. She takes him, reluctantly; it is a crime scene. As he looks around, Jack says goodbye and realizes that he no longer feels an attachment to it. They begin the rest of their lives.