A woman nicknamed Johnsy has come down with pneumonia, and is now close to death. Outside the window of her room, the leaves fall from a vine. Johnsy decides that when the last leaf drops, she too will die, while her best friend Sue who stays with her, tries to tell her to stop thinking so pessimistically.
In the same apartment building, an elderly, frustrated artist named Behrman lives below Johnsy and Sue. Behrman has been claiming that he will paint a masterpiece, even though he has never even attempted to start. Sue visits Behrman, telling him that Johnsy, who is dying of pneumonia, is losing her will to live. Sue tells Behrman that Johnsy claims she will die when the last leaf falls off of the vine outside her window. Behrman scoffs at this as foolishness, but—as he is protective of the two young artists—he decides to visit Johnsy and see the vine from her window.
In the night, a very bad storm comes and wind is howling and rain is splattering against the window. Sue closes the curtains and tells Johnsy to go to sleep, even though there is still one leaf left on the vine. Johnsy protests against having the curtains closed, but Sue insists on doing so because she doesn't want Johnsy to see the last leaf fall. In the morning, Johnsy wants to see the vine to be sure that all the leaves are gone, but to their surprise, there is still one leaf left.
While Johnsy is surprised that it is still there, she insists it will fall that day. But it doesn't, nor does it fall through the night nor the next day. Johnsy believes that the leaf stayed there to show how wicked she was, and that she sinned in wanting to die. She regains her will to live, and makes a full recovery throughout the day.
In the afternoon, a doctor talks to Sue. The doctor says that Mr. Behrman has come down with pneumonia and, as there is nothing to be done for him, he is being taken to the hospital to be made comfortable in his final hours. A janitor had found him helpless with pain, and his shoes and clothing were wet and icy cold. The janitor couldn't figure out where he had been on that stormy night, though she had found a lantern that was still lit, a ladder that had been moved, some scattered brushes, and a palette with green and yellow colors mixed on it. "Look out the window, dear, at the last ivy leaf on the wall. Didn't you wonder why it never fluttered or moved when the wind blew? Ah, darling, it's Behrman's masterpiece - he painted it there the night that the last leaf fell."