Burmese Days is set in 1920s imperial Burma, in the fictional district of Kyauktada. A Burmese magistrate by the name of U Po Kyin is planning the destruction of the career of Indian Dr. Veraswami. The only thing that could possibly give the doctor any chance in this struggle is his friendship with European John Flory who - as a white man - has higher prestige. U Po Kyin begins his campaign by sending libelous, anonymous letters with false stories about the doctor and he even sends a subtly threatening letter to Flory.
Meanwhile, the niece of Mrs. Lackersteen, Elizabeth, arrives in Burma. When Flory meets her, he is immediately taken with her and the two develop a close friendship. As Elizabeth expects, Flory is about to ask her to marry him, but is disrupted by Mrs. Lackersteen and subsequently an earthquake. Mrs. Lackersteen interrupted the two on purpose as she has discovered that a military police officer named Verrall is arriving in Kyauktada and wishes for Elizabeth to marry him. So, Mrs. Lackersteen tells Elizabeth that Flory is keeping a Burmese woman. Elizabeth indeed does fall for the rather rude Verrall and Flory is devastated.
Meanwhile, U Po Kyin has developed a plan to be elected to the European Club in Burma as they are forced to elect a native member. U Po Kyin plans to start a rebellion and blame it on Dr. Veraswami. The rebellion is indeed started and a native rebel is killed by acting Divisional Forest Officer, Maxwell. A few days later, the Europeans discover the body of Maxwell. This creates a tension between the Burmese and the Europeans and a large riot begins the following week. U Po Kyin planned to stop the riot and become a hero in the eyes of the Europeans, but his plot is foiled when the riot is stopped by Flory instead. Flory becomes a hero and Dr. Veraswami's prestige is restored.
Verrall leaves Kyauktada without even saying goodbye to Elizabeth and she falls for Flory again. Flory is happy and plans to marry Elizabeth. However, U Po Kyin has not given up; he hires Flory's former Burmese mistress to create a scene in front of Elizabeth at the church sermon. Flory is disgraced and Elizabeth leaves him. Overcome by the loss, Flory commits suicide. U Po Kyin's plans have succeeded, Dr. Veraswami is demoted and sent to a different district and U Po Kyin is elected to the Club. He plans to redeem his life and cleanse his sins by financing pagodas, but he dies before they are constructed. Elizabeth marries another club member named Macgregor.