Mine Boy opens with Xuma arriving in the impoverished and mostly black Johannesburg slum of Malay Camp. Xuma is a farm boy who has come from the economically depressed north in search of work in a gold mine. With no money and nowhere to stay, Xuma is taken in by Leah, an illicit beer seller. At Leah's, Xuma meets Daddy, Ma Plank, Joseph, and Dladla, all of whom confuse him with their drunkenness, violence, and apparent lack of beliefs. In exchange for a room and food, Leah expects Xuma to use his considerable size and strength to assist her. Xuma is confused by her kindness, but appreciates that she takes a shine to him.
Xuma wakes up to discover that two women are fighting out in front of Leah's while a crowd watches eagerly. Leah breaks up the fight and takes the injured women to her house to rest. An employee of Leah's named Joseph takes Xuma out walking; it is Saturday—a holiday for black people in Johannesburg, who have received their wages and so are spending money on shopping, drinking, and gambling. A police van suddenly arrives and people scatter. Xuma refuses to move, saying that he has done nothing wrong. However, a white police officer strikes Xuma with his stick, causing Xuma to knock the officer out with a punch. Xuma runs away and is led to safety by a colored man (a mixed-race South African) who hides him in his house until the police give up their search.
Xuma returns to Malay Camp later that day; Joseph and Leah are relieved, but they caution him to run in the future. Leah takes Xuma for a walk and he witnesses her give a black policeman a bribe to keep her updated about planned raids of beer sellers. That evening Xuma meets Eliza, Leah's niece. He is immediately drawn to her beauty. They go out on a walk together up a hill outside of town. In the distance Xuma sees a hill and Eliza explains that it is a mine dump—white sand dug out of the gold mines. Xuma attempts to kiss her, but she runs away, leaving Xuma confused and angry.
The next day Xuma and Johannes walk to the mine, where Johannes can get him a job. A white man at the mine commands Xuma to push a truck full of sand that usually requires the work of two men. Xuma manages to move the truck, but injures his leg on the axle. Xuma's boss, a white Irishman with red hair named Paddy, brings him to the mine site doctor for bandaging. Paddy tells Xuma that he will be his righthand man and will lead a group of miners, whom he must threaten with violence if they do not cooperate.
Back at Malay Camp, Xuma finds Eliza has brought another man home—a fellow teacher who dresses and speaks like a white man. Xuma meets Maisy, who takes a liking for him. He goes out dancing with Maisy but his mind is preoccupied with thoughts of Eliza. That night, Eliza goes to Xuma's room and they kiss. However, Eliza becomes conflicted and admits that she has assimilationist aspirations: though she is black, she does not feel black inside. She wants to be like white people, and wants a man who shares her aspiration.
Months pass. Xuma has his own room in Malay Camp, having needed to get away from Leah's and his obsessive thoughts about Eliza. One night he meets his boss Paddy and his girlfriend Di on the street. They invite him to dinner, but he is reluctant to be friends with a white man. Reluctantly Xuma goes up, and he feels uncomfortable to be in such a nice apartment full of white men's modern conveniences, such as electric lights and central heating. While Paddy is out of the room, Xuma confides in Di about Eliza. After Xuma's departure Paddy tells Di that Xuma will grow into a strong leader who will fight back against racial oppression, but Di feels differently: she speaks of Xuma as though he is not fully human.
One night Xuma returns to Leah's place, where he and Eliza confess their love for one another before having sex. Xuma falls asleep happy, but in the morning Eliza is cold and tells him that the night before was a mistake. Feeling blank and confused, Xuma turns to Maisy for comfort. They travel to Hoopvlei, a town outside Johannesburg. During the pleasant Sunday outing, Xuma contrasts Maisy's embrace of life with Eliza's cold, reserved nature. After taking a taxi back to Malay Camp, Maisy puts Xuma to bed in her room at her employer's house, where she works as a maid.
Maisy wakes Xuma very early in the morning and he leaves for work. Johannes tells him that Dladla is informing on Leah to the police and Paddy informs Xuma that their crew will be on shift for a month. Xuma and Paddy notice a trickle of water compromising the tunnel's structure, but an engineer inspects it and says the mine shaft is safe to work in. Xuma notices a worker is coughing up blood. The man explains that he needs to keep working because he is in debt to a white man and is afraid of losing his family's property. To Xuma's surprise, Paddy steps in and has the man assessed by the mine doctor. Having been diagnosed with lung sickness, the man is entitled to a severance payout that covers his debts and a train ticket back to his family. The man rejoices but immediately begins coughing up more blood.
After work Xuma and Maisy go to inform Leah about Dladla. At Malay Camp, he runs into Eliza, who confesses her love for him. Xuma is delighted and agrees to take her in as his woman. Leah throws a party that night to celebrate the couple and give them her blessing. Thereafter, Eliza moves into Xuma's room and they establish a comfortable domestic life. But the period of happiness does not last long: soon Daddy, another one of Leah's boarders, dies from internal injuries after being struck by a car. Eliza does nothing to comfort Leah in her grief, and after one more night of lovemaking with Xuma, she leaves him in the night to take a train ride away from Malay Camp, asking Ma Plank to deliver the news to Xuma in the morning. Soon after, Leah is arrested for beer selling after a successful sting operation by local police.
The tragic and confusing events lead Xuma into a depression. After Leah's trial, Paddy notices Xuma's anger and attempts to sympathize. However, Xuma does not believe a white man could possibly understand the oppression and injustice he has dealt with. Paddy tries to explain that he cares despite his race, and discusses the idea of thinking of himself as a man first and a black or white man second. After some resistance, Xuma begins to imagine what it would be like to live in a society without color, where people were people, and not divided into a hierarchy by color. Xuma falls asleep inspired by the images and ideas passing through his mind.
The next morning, Xuma returns to work at the mine, only to discover that the shaft has collapsed. Chris and Johannes had held the roof while the workers escaped, and had become trapped in the process. Xuma and Paddy go underground, returning soon after with Chris and Johannes dead in their arms. The manager and the engineer try to attribute the losses to unnecessary panics and order the remaining miners to go underground and work again. Xuma grows furious and demands that repairs be made first; the workers side with Xuma and so does Paddy. In response to the workers' strike, the mine management calls in the police, who swarm in to attack the striking miners. In his panic, Xuma escapes, running all the way to Maisy's employer's house to tell Maisy what has happened and how he imagines becoming a man without color. Xuma says he will turn himself in, because it will be good for a black man to tell the white people how he feels. He then promises Maisy that he loves her and asks her to wait for him to be released from prison. Together, they walk toward the police station. The novel ends with an ominous image of Malay Camp and Johannesburg going dark at night, leaving the question of Xuma's fate unanswered.