The novel starts off in a summer in the 1950s in New York City, where Esther Greenwood, the narrator has arrived. Esther has just won a scholarship and is now interning for a fashion magazine called Ladies Day for a month, all expenses paid. She is one of twelve people who has been given this opportunity. The first person Esther gets close to is Doreen, another scholarship winner, whose sarcastic personality probably plays a part in it. Esther’s new friend takes her out to drink and they’re approached by many men, one of whom is a DJ by the name of Lenny Shepherd.
The girls agree to go to his apartment and once there, Doreen and Lenny start to get more and more sexually intimate. Esther eventually leaves, not wanting to witness what they’re doing any longer, and she goes back to the hotel they have been put up in, wishing she could erase what she saw. Much later in the night, Lenny drops off a puking Doreen at Esther’s door, and she takes care of her despite no longer wanting to be her friend.
In the morning, Esther goes to a Ladies Day banquet with the other interns. Afterwards, the editor of the magazine, Jay Cee, enquires about Esther’s plans for after she graduates college, even though she’s just finished her first year. Esther tells her she’s not sure yet of her plans and Jay Cee shows dislike for what she thinks is a carefree and reckless attitude. Despite this, Jay Cee tries to tell Esther it’s okay and that she shouldn’t let the big city get to her. The interns go to a movie together after which they all start getting sick. It turns out they all have food poisoning after eating at the banquet earlier that day. All except Doreen, who didn’t attend.
Esther’s ex is a Yale medical student called Buddy Willard. His mother has set up a meeting for Esther with Constantin, who works at the United Nations as an interpreter. He calls her and asks to meet at a restaurant. Esther has come to hate Buddy for the hypocrite that he is as well as his patronizing behavior towards her. He had expected Esther to remain faithful and devoted to him after he himself had cheated on her with a waitress. Esther is happy with the karma he has been served, he’s a med student who is confined to a hospital while recovering from TB. Meeting Constantin and seeing him work instills a sudden fear of what she will do in the future in Esther. Esther is enticed by the idea of losing her virginity to Constantin that night, but all they end up doing is sleeping beside each other in his apartment. Esther thinks back to how Buddy proposed to her in the sanatorium he is in now. She turned him down because she didn’t want to get married.
A photo session is held for all the contest winners at Ladies Day towards the end of the month. The concept is that every intern must pose with props that signify what they want to be one day. This sends Esther into a panic because she can’t decide what to do. Jay Cee says Esther wants everything and she finally settles on being a poet. However, when the shoot begins, Esther starts to cry hysterically in front of everyone. Just a few days before they all leave, Esther goes on a date set up by Doreen with a Peruvian man named Marco who she starts to think is a ‘woman-hater.’ Marco tries to rape Esther but she fights back and is able to escape.
Esther comes home from her internship and is immediately greeted with bad news; she wasn’t accepted into the writing course she applied for and would now have to spend the rest of her summer at home in the Boston suburbs. Esther contemplates going to stay with her Harvard friends like she would have if she had gotten the writing course but then decides against it. Instead, she wants to get through the infamous Finnegans Wake and also get ahead on her thesis. Very soon after, she decides to stop that and quit college completely. After many sleepless nights, she pays a visit to the family doctor for some pills to help her sleep but instead gets referred to a psychiatrist.
Dr. Gordon seems to have his life perfectly put together, as a young man with a family who’s doing well for himself. At one of her sessions, he asks Esther if it would be okay for him to speak to her mother. To Mrs. Greenwood, the Doctor suggests electro-shock therapy for Esther, who has now become almost obsessed with the thought of suicide.
The institution Esther goes to for the shock treatments feels strangely out of place for her. This shows Esther is losing touch with reality, she doesn’t feel like the people there are real; they seem fake. The treatments are something Esther comes to detest, so she says to her mother that she wants to stop them and also not see Dr. Gordon anymore. All her mother says is that she didn’t think Esther was like those bad people in the place where they went for the treatments. A little while later, Esther draws a hot bath for herself because she decides to she’s going to commit suicide by cutting her wrists, but she can’t go through with it in the end.
Next, Esther contemplates suicide by hanging but she soon finds out that their house’s build doesn’t allow for that. Then she plans on drowning herself when she’s with her friends, but again, can’t bring herself to do it when the time comes. At last, Esther leaves her mother a note saying she’s going out for a walk. What she actually does instead is swallow a bottle of her sleeping pills. When she comes to her senses, she thinks she’s lost her eyesight, but it was just the room that was dark. During recovery, a lot of people come to visit Esther, but she doesn’t want the attention and so behaves belligerently with them and also towards the nurses caring for her. She’s also told by many of the nurses that she’ll be okay when she goes to ‘you-know-where.’
Esther doesn’t end up going to the state-run mental institution because she gets funding instead to go to a private one by philanthropist Philomena Guinea, who comes to know about Esther trying to kill herself through press coverage of it. Esther’s room in the facility is in the Caplan wing. The woman who treats her is Dr. Nolan, who Esther feels is a mix of Myrna Loy and her mother. This time around, she’s promised she won’t be given electro-shock therapy, but if it’s deemed necessary, she will be notified beforehand. Esther is surprised by another ex of Buddy Willard’s, Joan Giling, who is there for the same reasons as her.
Dr. Nolan stops allowing Esther visitors because she worries that she isn’t getting much better. Esther is actually very happy with this decision because she despises the visits she has been getting from Philomena Guinea, old friends who pity her and most of all, the ones from her mother. Esther expresses hating her mother to the Doctor who smiles in response.
Both Esther and Joan are moved to a different ward called Belsize. The patients here seem much fancier and more well-dressed. Esther starts getting shock treatments again but it’s much better this time around. She also buys contraceptive pills so she has the freedom to do what she wants without having to end up marrying someone like Buddy.
Joan is let out of the facility and Esther goes to see her. While there, she meets a young professor of Mathematics at Harvard called Irwin. Esther seduces him and they sleep together, but afterwards, she starts to bleed profusely. Irwin drops her off at Joan’s who takes her to the hospital to get treated for the hemorrhaging. She goes back to the facility, and Joan ends up coming back as well. Very soon after that, Esther is awoken with the news that Joan has gone missing, after which she is found dead in the woods. Joan committed suicide.
The time comes for Esther to leave the facility herself, with the new semester starting in January. She doesn’t want to go back home in between, so she stays until she can go back to the dorms directly. She reflects on how the people at college will act differently around her than before. Even her own mother can’t face the reality that her daughter is mentally ill; she prefers instead to think of Esther’s treatment there as a sort of “bad dream.” Of all people, Buddy Willard comes to pay Esther a visit at the facility. He asks her if something about him makes women crazy, since both Esther and Joan; ex-girlfriends of his, ended up in the mental institution. Esther’s only response to this is laughing out loud.