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In 1961, Elizabeth Zott prepares her daughter Mad's school lunch before leaving to present her wildly popular TV show, "Supper at Six." It’s a job she took under some protest, and it was the unexpected consequence of confronting the executive Walter Pine at the station KCTV over his daughter eating all of Mad’s lunches. Impressed by Elizabeth, who is young, beautiful, and very assertive, Walter quickly offers her a regular role as a TV host. Elizabeth needs a steady paycheck, so she reluctantly accepts.
A flashback to 1952 shows Elizabeth in her career as a chemist at Hastings Research Institute in Commons, California. She’s there working on abiogenesis, having left UCLA’s doctoral program before getting her PhD. She was compelled to quit the program when her supervisor Dr. Meyers cornered and raped her and she defended herself by stabbing him with a pencil. At Hastings, she’s treated as a second-class citizen and rarely appropriately credited for her work. She meets renowned chemist Calvin Evans, who initially mistakes her for a secretary when she bursts into his well-supplied lab in search of beakers. Despite a rocky start, in which they initially try to be platonic colleagues, they develop a research partnership and quickly fall deeply in love. Calvin and Elizabeth do their best to navigate the unfriendly and toxic work environment at Hastings, where their relationship places them both under intense scrutiny. Elizabeth cooks for Calvin and herself every day, using her chemical expertise and patience to repeat experiments to perfect her dishes.
Calvin proposes, but Elizabeth refuses to marry him, as she doesn’t want to sacrifice her career by taking his name. She finds and adopts a stray dog whom she names Six-Thirty, and she and Calvin take up rowing together. Everything seems to be going well until Calvin dies suddenly in an accident. Elizabeth, who discovers she’s pregnant shortly after he passes away, faces even worse treatment at work and is eventually fired. Unable to go back to Hastings, she turns her kitchen into a lab, continuing her abiogenesis research while consulting and copy-editing for former Hastings colleagues. She gives birth to her daughter, whom she christens “Mad Zott,” but tells people her name is Madeline. With help from her kind neighbor Harriet Sloane and support from her obstetrician and rowing coach Dr. Mason, Elizabeth tries to balance raising a baby, making enough to keep the lights on, and performing and publishing her research. She returns to Hastings, but Dr. Donatti refuses to give her either the research she and Calvin worked on together or access to her own lab. She’s forced to do menial work as a lab tech. After a nasty confrontation, the usually hostile office manager Frask reveals that she was also sexually assaulted and prevented from finishing a PhD. Frask has been fired for gaining weight, but before she leaves, she passes on Calvin’s files to Elizabeth. When Elizabeth discovers that Donatti has been plagiarizing her work, as have several of her other male colleagues, she quits Hastings—she believes—for good. The narrative then returns to 1961, where Walter Pine offers her the job presenting a cooking show and she quickly accepts.
Phil Lebensmal, Walter Pine’s superior at KCTV, insists that Elizabeth’s frank attitude be reined in on live TV. He wants her and “Supper and Six” to be light, fluffy, and sexy. Elizabeth disagrees; she dismisses every tight and revealing wardrobe choice, refuses to read any of the cue cards Walter writes, and describes her cooking processes with a sharp, matter-of-fact scientific demeanor that the studio executives hate. Despite Lebensmal’s anger, the show quickly becomes immensely popular, especially among housewives, who appreciate Elizabeth's intelligent and unpatronizing approach. Meanwhile, Harriet Sloane—Elizabeth’s friendly but lonely neighbor—has been looking after Mad while Elizabeth works. One day Harriet lets some information slip about Calvin when Mad is working on a family tree project for school. Mad's pursuit of more information about her dad leads her to Reverend Wakely, a longtime pen-pal of her father’s. He assists her in investigating the orphanage where Calvin was raised. During Wakely’s inquiries, the dishonest bishop who runs the home unwittingly discloses that Calvin’s parents were involved in Calvin’s upbringing. The Parker Foundation is a foundation with lots of money to donate to worthy causes, and unbeknownst to Calvin, is a family connection through his mother. The priest lied to the representative of Calvin’s family who came to the boys’ home when he was young, correctly guessing that the grieving family would donate money to All Saints in his name.
On air, Elizabeth offends a sponsor by calling their products trash and refusing to use them. This prompts Lebensmal to summon her, and when she’s alone in his office, he aggressively fires her and then tries to sexually assault her. She responds by pulling out her chef’s knife from her handbag, which shocks him so much he has a heart attack. She discovers that he’s been hiding sponsorship offers and advertising deals for the show, and while Lebensmal recovers in hospital Walter Pine is promptly instated as his replacement.
Elizabeth gets an offer from Life magazine for an interview. She’s initially uninterested, but Harriet and Walter convince her to take them up on it. She shares her entire backstory, including her sexual assault and her feelings about Calvin’s death, with a very surprised reporter named Franklin Roth. He writes an article highlighting her scientific work. However, the piece gets distorted before publication. Elizabeth’s physical attributes and “charm” totally eclipse her accomplishments after Roth’s editor makes changes. She becomes extremely depressed, feeling useless and betrayed. Roth resigns from Life and tries to publish the truthful account elsewhere, leaving a copy of the original article at Elizabeth’s house where Mad finds it. She gives it to Frask, now a typist for Reverend Wakely. Frask, infuriated by what Life left out, publicly denounces the misleading article. Roth’s original is then picked up and published by Vogue.
Still hurt about the article’s diminishment of her life’s work, and after conferring with Wakely, Elizabeth decides to leave “Supper at Six” to pursue research in abiogenesis again. Although she has no job offers when she begins looking, Frask eventually invites her back to Hastings. The Parker Foundation wants to hire her, and knows about Donatti's wrongdoings, including years of financial misdeeds and all of his plagiarism. Hastings promotes Frask and dismisses Donatti, offering Elizabeth the head of chemistry position. Avery Parker, founder of the Parker Foundation, then comes forward and reveals that she is Calvin’s biological mother. She had to give him up at birth because of family pressure, as she was unmarried. When Avery discovered the bishop's deceit about Calvin's death as a child, she tried to reconnect. Although she never met her son before he died in the accident, she wants to build a relationship with her granddaughter Mad. The novel ends with Elizabeth warmly welcoming Avery, inviting her to come to “supper at six” at their house, and re-engaging with her chemistry research in her lab at Hastings.
