The novel begins with the narrator describing the life and work of the artist Charles Strickland. The narrator discusses the uniqueness of Strickland's work and the intensity of his life. He talks about the nature of greatness as well as the struggle to accurately perceive it in Strickland. He says that while Strickland is now viewed as a major artist, he did not see him that way when they first met.
The main narrative starts with the narrator talking about his time in London in various artistic circles. He says he encountered a woman named Amy Strickland who said that her husband, Charles, was a very unremarkable stock broker, but a dependable husband and father. The narrator says that after having dinner with him one night, this was his entire impression of the man. However, this impression is quickly upended when the narrator learns that Strickland has abandoned his wife and children. The narrator visits Amy, where she tells him Strickland has departed for Paris and left a shockingly brief note saying he is not returning and is providing them with nothing. Amy's brother, Colonel MacAndrew, is enraged by this behavior. They ask the narrator if he will seek out Strickland when he goes to Paris and the narrator, somewhat reluctantly, agrees.
Traveling to Paris, the narrator finds Strickland living in a run-down hotel. His appearance is unkempt and his living situation is meager, but he appears to be largely happy with his decision. The narrator presses him about his decision to desert his family, but he shows no indication of guilt or remorse. His response repulses and fascinates the narrator. After arguing briefly, Strickland asks the narrator to join him for dinner. While they are at the restaurant, a woman shows interest in Strickland, but he harshly rejects her. The narrator returns to London and tells Amy that Strickland has not taken up with another woman, but rather has dedicated himself entirely to painting. She says this news makes her certain he will not return. She takes up work as a typist to support her family. The narrator does not see Strickland for several years.
The narrator travels to Paris and meets up with his friend Dirk Strove, a painter. He describes Dirk as a kind man with a strong critical eye, but a very mediocre painter. The narrator goes to Dirk’s house and meets his wife, Blanche. Dirk loves her intensely, but she merely seems to treat him with charity. They all talk and eventually the narrator learns that Dirk knows Strickland. Dirk thinks he is a strange but extremely talented person. His wife adds that Strickland brutally insulted Dirk's paintings when he came to their house to ask for money one day.
The narrator reconnects with Strickland, finding him to be the same cold and indifferent person he remembered. He also begins to spend time with Strickland and Dirk together, with Strickland mocking Dirk constantly and Dirk swearing to never see him again, only to relent a few days later. This continues on for some time until Strickland becomes extremely sick. After not hearing from him for a few days, Dirk and the narrator travel to his apartment to see what is wrong. They discover that Strickland is deathly ill. Dirk insists on bringing him to his home to nurse him back to health, against his wife's wishes.
Strickland recovers at Dirk's home, showing no gratitude for Dirk's kindness. The narrator is disgusted by Strickland's cruelty as well as Dirk's obsequious behavior. Strickland eventually recovers and subsequently runs off with Blanche, who leaves Dirk and refuses to speak to or acknowledge him after the fact. Dirk is devastated by this loss, but seems to bear no ill will towards Blanche, confounding the narrator. Later, Dirk comes to the narrator and tells him that there has been a terrible incident. Blanche has attempted suicide after being deserted by Strickland. She is hospitalized for a few days and subsequently dies. Distraught, Dirk decides to return home to Holland. The narrator wishes him well.
Shortly thereafter, the narrator runs into Strickland. He treats him coldly, but Strickland still remains unaffected, asking if he would like to play chess. He again shows no remorse for the effects of his behavior. He tells the narrator that he was only interested in Blanche physically and as a model for his paintings. He also adds that Dirk took Blanche in after she became pregnant out of wedlock and that their marriage was less of a romantic relationship and more of a formal arrangement. They part ways and the narrator says he never encountered Strickland again.
The third part of the book begins with the narrator talking about his attempts to piece together the rest of Strickland's life. He learns that Strickland spent the last years of his life in Tahiti and stopped briefly in the port city of Marseille. In Tahiti, the narrator meets a man named Captain Nichols who tells him he met Strickland in Marseille. There, they spent a great deal of time in seedy bars and restaurants, having various minor adventures. Nichols recounts Strickland's conflict with an intimidating local man named "Tough Bill." On a beach, Bill asks for papers that Strickland had been given and Strickland refused. Later that evening, in a bar, the two got into a fight after Bill spit in Strickland's face and Strickland threw a bottle at him. The fight ends, but Nichols worried for Strickland's safety, as Bill was a vindictive man. Strickland received passage on a ship bound for Australia and Nichols did not see him again. The narrator notes that while this story is exciting, its degree of truth is questionable, as Nichols is a known liar.
Following his encounter with Captain Nichols, the narrator meets Tiare Johnson, the manager of a hotel where he lives for a time. Tiare also knew Strickland and tells the narrator about Strickland's final years in Tahiti. Strickland married a local woman named Ata and they had two children together. Strickland appeared to be relatively happy, enjoying a different pace of life and painting often. This came to an end, however, when he contracted leprosy. The narrator learns from a doctor named Mr. Coutras that Strickland's illness left him horribly disfigured and in immense pain. It also left him, Ata, and their children shunned by the native community. One of Strickland's children died and Strickland himself perished shortly after. Before dying, he painted his greatest work on the walls of his house and then insisted his wife destroy it after his death. Some years later, the narrator returns to London and tells Amy about her husband's final years. The book ends with the narrator reflecting on Strickland's struggle to reach for the divine in his art.
