In May of 1899, in a small Greenwich Village restaurant, Sue and Johnsy meet. They become friends and rent an apartment together to share expenses.
In November, Johnsy becomes ill with pneumonia. Her illness lingers. She becomes frail and loses hope of recovering. Outside her window is an old ivy vine on which only a few leaves remain. Johnsy has become so disheartened that she refuses to fight her way back to health and convinces herself that when the last leaf falls off the vine, she will die.
It is the day of "house calls" for doctors, and the doctor tells Sue that if Johnsy is to get well, she must get her mind on something other than her sickness. Sue is worried; she goes downstairs and reveals her fears to Mr. Behrman, a grizzled, unsuccessful artist who dreams of one day painting a masterpiece. Only one leaf remains on the vine now, and even Mr. Behrman is worried that tonight it will fall victim to the wind and rain.
The next morning, when Sue and Johnsy look out the window, the last leaf is still there. Johnsy thinks about her situation and convinces herself that fate caused the leaf to stay on the vine so that she would not die. With this change in attitude, Johnsy gradually gets well. The doctor comes and verifies Johnsy's recovery. The doctor also tells Sue that Mr. Behrman has pneumonia and is beyond help. He dies that same day.
Later that day, Sue discovers how Mr. Behrman became ill. She tells Johnsy that on the stormy night when the last leaf was about to fall, Mr. Behrman took a ladder, climbed the wall, and painted a true masterpiece--a picture of the last leaf on the brick wall.