From childhood, Brooklyn teenager Natalie Miller, who has upper front teeth that are slightly bucked, and a nose too large for her face, has considered herself to be homely, and has never subscribed to her mother’s determined belief that she will grow up to be pretty. By contrast, her best friend, Betty, is a popular and beautiful blonde cheerleader who has been going steady with the handsome Stanley since junior high school. Natalie’s efforts to become a cheerleader herself, impress a blind date, and attend her graduation dance all fail. She is briefly cheered up by her beloved Uncle Harold, who tells her that someday a man will look beyond her face, and see her good inner qualities, but she becomes disillusioned after Harold gets engaged to a sexy, voluptuous go-go dancer, Shirley. Believing that Harold chose Shirley based on her looks, Natalie regards Shirley with contempt, and when Harold dies suddenly, avoids attending his funeral.
A year later, Natalie encounters Shirley, who has turned to drugs in her grief over Harold. Natalie sees that Shirley and Harold really did love each other, and that Shirley’s physical attractiveness has not brought her happiness. Natalie’s parents worry because she has been expelled from college, has not found a job, and has no boyfriends or marital prospects. They try to arrange dates for her, and her father attempts to bribe Morris, an unattractive aspiring optometrist, to marry her. After learning of the bribery scheme, an incensed Natalie moves out of her parents’ apartment, planning to move in with Shirley in Manhattan.
Upon arriving at Shirley’s bohemian apartment building in Greenwich Village, Natalie finds that Shirley has committed suicide. Natalie rents and fixes up Shirley’s vacant apartment, and gets a cocktail waitress job at the “Topless Bottomless Club”. Natalie is attracted to her downstairs neighbor, David Harris, an architect, who has left his job for three months to pursue his dream of becoming a painter. Having dismissed David as a “sex pervert” because he is usually painting beautiful nude female models, she is taken aback when David finds her face “interesting” and asks her to model for him. Their friendship gradually grows into a romance, with Natalie encouraging his painting aspirations and David building her self-confidence. However, just after Natalie sees her old friend, Betty, make an unhappy marriage due to an out-of-wedlock pregnancy, Natalie discovers David is actually married to a wealthy, beautiful woman and has two young sons.
After a confrontation, David reassures Natalie that he really loves her and he will go back to his family home, end his marriage, and return to her. At first Natalie waits eagerly in his apartment for his return, but as time goes by she feels guilty about separating him from his family. Finally she writes David a farewell letter, saying she will always love him but expressing the wish to take responsibility for her own happiness, and leaves.