Living in early 20th century Greenwich Village are two young women artists, Sue and Johnsy (familiar for Joanna). They met in May, six months previously, and decided to share a studio apartment. Stalking their artist colony in November is "Mr. Pneumonia." The story begins as Johnsy, near death from pneumonia, lies in bed waiting for the last leaf of an ivy vine on the brick wall she spies through her window to fall.

"I’m tired of thinking," says Johnsy. "I want to turn loose my hold on everything, and go sailing down, down, just like one of those poor, tired leaves"(16). However, an unexpected hero arrives to save Johnsy. It’s not the brusque doctor who gives her only one in ten chances to survive, raising them to one in five if Sue can get her to hope for something important like a man, not her true desire to "paint the Bay of Naples some day" (14).

Mr. Behrman, an old man who lives in the apartment below Sue and Johnsy, who enjoys drinking, works sometimes as an artist’s model, and as yet has made no progress over the past 40 years on painting his own masterpiece, becomes in typical O. Henry fashion the hero. The evidence of his heroics are found the day before he dies from pneumonia: outside Johnsy’s window are a ladder, a lantern still lighted "some scattered brushes, and a palette with green and yellow colors mixed on it . . . it’s Behrman’s masterpiece--he painted it [a leaf] there the night that the last leaf fell"(19), Sue informs Johnsy.