Setting: The action takes place in the early 20th century in and around Butterfly's house on a hill near Nagasaki, Japan.

Lieutenant B.F. Pinkerton, an officer in the U.S. Navy, is captivated with Cio-Cio San, a young geisha. Pinkerton's desire for Butterfly is so strong that he would do anything to have her. He therefore arranges through Goro, a marriage broker, to marry her in a Japanese wedding ceremony.

Sharpless, the American Consul at Nagasaki, recognizes that Pinkerton is not truly in love with Butterfly, but rather is entranced by the young geisha's fragile beauty and innocence. Sharpless also recognizes that Butterfly truly loves Pinkerton, and he warns Pinkerton not to marry her. Pinkerton, overwhelmed with desire for Butterfly, dismisses Sharpless' warnings, and the marriage ceremony is performed. Together, Butterfly and Pinkerton face the scorn of her family, and the foreboding caution of Sharpless, who realizes the improbability of the union.

Pinkerton is called back to America and Butterfly patiently and confidently waits for him to return to Nagasaki. She is kept company throughout her long vigil by Sorrow, her son by Pinkerton, and her handmaiden Suzuki. Eventually, Pinkerton returns to Nagasaki. But it is not the joyous reunion of which Butterfly had dreamed. She is devastated to hear that Pinkerton has arrived on the shores of Nagasaki with a new American wife. In anguish and despair, the heartbroken Butterfly ends her life.