In 1953, Esther Greenwood, a 19-year-old undergraduate student from the suburbs of Boston, is awarded a summer internship at the fictional Ladies' Day magazine in New York City. During the internship, Esther feels neither stimulated nor excited by the work, fashion, and big-city lifestyle that her peers in the program seem to adore. She finds herself struggling to feel anything at all aside from anxiety and disorientation. Esther appreciates the witty sarcasm and adventurousness of Doreen, another intern, but she identifies with the piety of Betsy, an old-fashioned and naïve young woman. Esther has a benefactor in Philomena Guinea, a formerly successful writer of women's fiction, who funds the scholarship through which Esther – from a working-class family – is enrolled at her college.
Esther describes in detail several seriocomic incidents that occur during her internship. In the beginning, she and Doreen meet Lenny, a gallant radio host who tries to seduce them, and who eventually dates Doreen. Another incident occurs with a mass food poisoning during a lunch thrown by the staff of the magazine. Much of the story is spent in flashbacks, where Esther reminisces about her boyfriend Buddy, whom she has dated more or less seriously, and who considers himself her fiancé. Esther's internal monologue often lingers on musings of death, violence, and the roles of women in her society. Shortly before the internship ends, she attends a country club party with Doreen, and she is set up with a wealthy Peruvian man named Marco who treats her roughly. Later, Marco takes her outside and tries to rape her; she breaks his nose and leaves. That night, after returning to the hotel, she impulsively throws all of her new and fashionable clothing off the roof.
Esther returns to her Massachusetts home that she shares with her widowed mother. She has been hoping for another scholarly opportunity once she is back in Massachusetts, a writing course taught by a world-famous author, but on her return, she immediately is told by her mother that she was not accepted for the course and finds her plans derailed. She decides to spend the summer potentially writing a novel, but she feels she lacks enough life experience to write convincingly. All of her identity has been centered upon doing well academically; she is unsure of what to make of her life once she leaves school, and none of the choices presented to her (motherhood, as exemplified by the prolific child-bearer Dodo Conway, Esther's neighbor, or stereotypical female careers such as stenography) appeal to her. Esther increasingly becomes depressed, and she finds herself unable to sleep. Her mother instructs her to see Dr. Gordon, a psychiatrist, whom Esther mistrusts because he is attractive and doesn't seem to listen to her. He prescribes electroconvulsive therapy (ECT); afterward, she tells her mother that she will not go back.
The ECT is ineffective, and Esther's mental state worsens. She makes several half-hearted attempts at suicide, including swimming far out to sea, then she makes a serious attempt. Esther writes a note for her mother that she "will go out on a long walk", crawls into a well-hidden hole in the cellar, and swallows many sleeping pills that had been prescribed for her insomnia. The newspapers presume her kidnapping and death, but she is discovered alive under her house after an indeterminate amount of time. She is sent to several different mental hospitals until Philomena Guinea, her college benefactor, supports her stay at an elite treatment center where she meets Dr. Nolan, a female therapist. Along with regular psychotherapy sessions, Esther is given huge amounts of insulin to produce a "reaction" (a common – and now disproven – psychiatric treatment at the time) and again receives ECT. Dr. Nolan ensures that they are properly administered. While there, she describes her depression as a feeling of being trapped under a bell jar, struggling for breath. Eventually, Esther describes the ECT as beneficial in that it has a sort of antidepressant effect; it lifts the metaphorical bell jar in which she has felt trapped and stifled. While there, she becomes reacquainted with Joan Gilling, who also used to date Buddy. The novel heavily implies that Joan is a lesbian and that she is attracted to, or interested in, Esther, who finds her strange.
Esther tells Dr. Nolan how she envies the freedom that men have and how she, as a woman, worries about getting pregnant. Dr. Nolan refers her to a doctor who fits her with a diaphragm. Esther now feels free from her fears about the consequences of sex; free from previous pressures to get married, potentially to the wrong man. Under Dr. Nolan, Esther improves. Various significant events, such as having sex for the first time, being hospitalized as a result, and Joan's suicide, provide her with a new perspective. Esther interacts with Buddy again toward the end of the novel when he visits her to ask if it was something about him that drove women to insanity, given that he dated both Joan and Esther. Buddy later wonders out loud who will marry Esther now that she has been hospitalized, effectively ending their commitment to get engaged. Esther feels relieved.
The novel ends with Esther entering a conference with her doctors, who will decide whether she can leave the hospital and return to school.
