The protagonist and viewpoint character is Sue. She shares a small flat in Greenwich Village with another young woman called Johnsy. Both are aspiring artists and both are having a hard time surviving in the competitive careers they have chosen. Sue's biggest problem when the story opens is caring for Johnsy, who has caught pneumonia and thinks she is dying. The old doctor who visits Johnsy tells Sue:
“She has one chance in—let us say, ten,” he said, as he shook down the mercury in his clinical thermometer. “And that chance is for her to want to live."
The only other character besides the two girls and the doctor is a temperamental old German named Behrman who talks in a heavy German dialect. He was once an aspiring painter but has lost hope and spends his time drinking gin. He earns a little money modeling for other artists, including Sue. She engages him to pose as an old miner for a series of sketches she is doing to illustrate a magazine story set in the West. He has to pose upstairs in the girls' flat where the light is better. Behrman has taken a paternal interest in these struggling young women and is terribly concerned about Johnsy.
He had been always about to paint a masterpiece, but had never yet begun it. For several years he had painted nothing except now and then a daub in the line of commerce or advertising. He earned a little by serving as a model to those young artists in the colony who could not pay the price of a professional. He drank gin to excess, and still talked of his coming masterpiece.
Johnsy adds to Sue's problems by believing that she is dying and obviously not caring. She keeps looking apathetically out their bedroom window at the old ivy vines growing up the side of a neighboring brick building. As the leaves keep dying off and falling in the cold winter wind, Johnsy imagines that she will die when the last leaf falls.
“Leaves. On the ivy vine. When the last one falls I must go, too. I've known that for three days. Didn't the doctor tell you?”
“Dear, dear!” said Sue, leaning her worn face down to the pillow, “think of me, if you won't think of yourself. What would I do?”
Susie's future is tied to Johnsy's. If Johnsy dies, Sue will probably give up the struggle and go back home to Maine, where opportunities for artists are nil. She would lose the companionship of her friend and would have no one to share the rent. So her need for Johnsy's recovery is practical as well as emotional.
But miraculously one of the leaves refuses to fall in spite of the wind and rain. Inspired by the resiliency of that brave leaf, Johnsy makes up her mind to recover from her pneumonia.
But, lo! after the beating rain and fierce gusts of wind that had endured through the livelong night, there yet stood out against the brick wall one ivy leaf. It was the last on the vine. Still dark green near its stem, but with its serrated edges tinted with the yellow of dissolution and decay, it hung bravely from a branch some twenty feet above the ground.
With Johnsy on her way to complete recovery, Sue confides to her that the leaf is not real. It was painted there in the middle of the stormy night by Old Behrman. And he died of pneumonia resulting from his exposure to the cold. But he had succeeded in creating the masterpiece he had been talking about painting for so many years, and he has also, through his artistry, transmitted some of his stubborn Germanic courage to the sick girl for whom he was willing to sacrifice his life.