Sue and Johnsy are two young female artists who share a studio apartment in the Greenwich Village neighborhood of New York City. A pneumonia outbreak is spreading across the city, and Johnsy is one of its victims. Concerned about her condition, her doctor and Sue convene in the hallway outside the apartment to discuss it privately. The doctor gives Johnsy a one-in-ten chance of survival. Those odds, he says, are only if Johnsy has the will to live, which he believes she does not. He asks if anything weighs on Johnsy’s mind, and Sue tells him that Johnsy wants one day to paint the Bay of Naples. The doctor ridicules the idea; he suggests that her reason for living should be something more serious and important than art, like a romantic relationship with a man. Sue tells him that “there is nothing of the kind” to report.

After the doctor leaves, Sue cries hard into a napkin, alone. She composes herself before entering the room where Johnsy rests. She carries her drawing board and whistles a happy tune. Johnsy faces the window, motionless.

Believing Johnsy to be asleep, Sue works on illustrating a story for a magazine. Like many young artists, she must work commercially to earn money. When Johnsy mutters something, Sue rushes to her side to find that Johnsy is counting backward from twelve. Sue looks out the window to see what her friend could be counting. All she sees is an old, nearly bare ivy vine clinging to the crumbling brick wall of the adjacent building. Johnsy continues her countdown, informing Sue that the vine is losing its leaves, and that when the last leaf falls, she will die.

Sue calls Johnsy’s idea nonsense, then she lies and says that Johnsy’s doctor gave her a ten-to-one chance of recovery. She encourages Johnsy to eat some broth so she can get back to her drawing. Sue needs to complete and sell the drawing to buy necessities. Johnsy says she doesn’t need it since she will be gone soon. Tired of life, her only wish is to witness the last leaf fall before she dies.

Sue convinces Johnsy to close her eyes and rest. She then goes in search of their downstairs neighbor, Mr. Behrman, who models for her. Behrman is an aging, failed artist with a European accent. He has had a forty-year painting career, yet he has never achieved success. He has never managed to begin his “masterpiece,” and he now paints only occasionally, making money by modeling for poor, young artists. He’s cantankerous and drinks too much, but he feels protective of Sue and Johnsy. Behrman scoffs when Sue talks about Johnsy’s thoughts about dying when the last leaf falls. The two return to the upstairs apartment, where they look fearfully at the fateful vine. As Sue sketches, a cold rain mixed with snow begins to fall.

The next morning, one solitary leaf unexpectedly remains on the vine, despite the night’s storm. Johnsy repeats her claim that when it falls, she will die. She expects it to fall during the day, yet it continues to cling to its stem. That night, the rain and wind resume.

On the second morning, Sue raises the shade, revealing that the last leaf is still there. After staring at it for a long time, Johnsy begins to perk up. She tells Sue that she has been bad and that the leaf has persevered to show her the wickedness of wishing for death. Johnsy requests food and a mirror, and she asks to be propped up in bed. She talks again of traveling to Italy to paint.

When the doctor arrives that afternoon, he again confers with Sue in the hallway. He now gives Johnsy a fifty percent chance of recovery. As he leaves, he remarks that he must attend to Mr. Behrman, who has also contracted pneumonia. The doctor has no hope for his survival.

The next day, the doctor tells Sue that Johnsy is no longer in danger and that she will recover. Sue informs Johnsy that Mr. Behrman has died. The building’s janitor discovered him two days earlier, soaking wet and in extreme pain. The janitor had also found a ladder and a lighted lantern, along with paints, a palette, and brushes. Despite the cold and rain, Behrman had gone outside to paint the final leaf on the wall, since the last leaf had already fallen. Sue calls the painted leaf “Behrman’s masterpiece.”