It is 1961, and Elizabeth Zott is the star of a successful television show called Supper at Six, which teaches viewers how to cook hearty and nutritious meals. Elizabeth began her career as a research chemist but was propelled to stardom when she confronted television producer Walter Pine because his daughter would eat her daughter’s lunch every day at school. Elizabeth’s daughter, Madeline, is a brilliant child who has read most of Dickens at the age of five. However, she wants to fit in with her classmates, as she sees that Elizabeth’s refusal to conform has made her very unhappy. Despite her fame and success, Elizabeth feels that her life is over.

Madeline’s father was a brilliant scientist called Calvin Evans, who worked with Elizabeth at the Hastings Research Institute in Commons, California, in the 1950s. Calvin fell in love with Elizabeth and wanted to marry her, but she felt that if they married, her achievements would always be subordinate to his. She also disliked the idea of having children; instead, the couple cared for a dog which followed Elizabeth home from a shopping trip one day. They called this dog Six-Thirty, a name that recalled the time when Calvin first asked Elizabeth about him, and she misheard and told him the time. While running to work with Six-Thirty on a leash early one morning, Calvin slipped in a puddle of oil and fell. He was then hit by a police car and died before an ambulance arrived. Only after his death did Elizabeth discover that she was pregnant with Madeline.

As an unmarried mother-to-be, Elizabeth was regarded as an embarrassment by the management of the Hastings Research Institute, who quickly fired her. The Head of the Chemistry Department, Dr. Donatti, took particular delight in doing this: he always disliked her, recognizing her brilliance as a scientist and shamelessly plagiarizing her work. After leaving Hastings, Elizabeth sank into depression, which was temporarily relieved when her daughter, Madeline, was born. However, Madeline cried continually, and Elizabeth initially found motherhood exhausting and frustrating. A neighbor, Harriet Sloane, saw how much difficulty she was having and offered to help. After some time, Elizabeth managed to form a strong bond with Madeline, treating her as a friend and equal and learning from her as much as she taught her. She insisted on reading complicated texts, such as Darwin’s Origin of Species, to Madeline, who quickly learned to read at an adult level. This disturbed her teacher, Mrs. Mudford, as did her requests for books by Norman Mailer and Vladimir Nabokov from the school library.

When Elizabeth begins her career as the host of Supper at Six, she has constant clashes with Walter Pine over the content and presentation of the show. She wants to focus on the science of preparing food, while he aims to produce mindless entertainment for bored housewives. However, Walter has some sympathy with Elizabeth’s viewpoint and is merely doing as he is told by his boss, a crass bully called Phil Lebensmal. One evening, after Supper at Six has aired, Lebensmal calls Elizabeth into his office and fires her. Enraged at the coolness of her attitude and the fact that she dares to argue with him, he thrusts his penis in her face and is about to assault her when she pulls a chef’s knife out of her handbag. Lebensmal has a heart attack, and Elizabeth discovers from the files on his desk that Supper at Six is a huge success and has received many syndication and sponsorship offers. As Lebensmal is forced to rest at home for at least the next year, Elizabeth and Walter are left in control of the show.

Many reporters want to interview Elizabeth, but she is only interested in talking to scientific journals. However, against her better judgment, she agrees to talk to Life magazine. Although the reporter, Franklin Roth, is impressed by Elizabeth and intends to write a sympathetic piece, his editor sends out other reporters to talk to Elizabeth’s father, who is in prison, her graduate supervisor at UCLA, who raped her, her former boss, Dr. Donatti, who plagiarized her research, and Madeline’s teacher, who dislikes her intensely. Between them, they provide the material for a scandalous article that sends Elizabeth into a deep depression.

Elizabeth decides to leave Supper at Six to devote herself to scientific research. Soon after this, she receives a call from the Hastings Research Institute, asking her to come in and meet a wealthy investor who wants to fund her research. This investor, Avery Parker, is the head of the Parker Foundation, which has acquired a majority shareholding in Hastings. Avery is also Calvin’s mother, who had been told that her son was dead and had only learned that he was alive when his profile started to appear in scientific magazines. He died before she could meet him, but she wants to become part of Elizabeth’s family and get to know her granddaughter, Madeline. Avery fires Dr. Donatti and gives Elizabeth his old job as Head of Chemistry, so she can begin the research on abiogenesis—the study of the original evolution of life—that she has always wanted to do.