It tells the story of Elizabeth Zott, who becomes a beloved cooking show host in 1960s Southern California after being fired as a chemist four years earlier.

[5] Garmus told People magazine that she wrote Lessons in Chemistry after her previous novel was rejected by 98 publishers because it was "too long".

[6] The book was originally called "Introduction to Chemistry", but was later renamed by the author's agent, Felicity Blunt.

[8] The book was inspired by Garmus's experience as a creative director in an advertising agency, in particular after a frustrating meeting where a male co-worker took credit for one of her ideas.

[6] After being sexually assaulted and refusing to apologize for stabbing her rapist, Elizabeth Zott is expelled from her doctoral program.

A month later, Zott adopts an abandoned explosive detection dog and names him Six-Thirty as that is the time he initially follows her home.

The head of the chemistry department, Dr. Donatti, approves her hiring but refuses to give her anything more than menial labor as a lab technician.

Pine, a local television producer, offers her a job as a cooking show host due to her unique personality.

Having been assigned a school project to make a family tree, Madeline searches for Evans's orphanage.

She meets Reverend Wakely during the project who recalls that he was pen pals with Evans during college and promises to call the orphanage for her and to look for its mysterious donor.

Zott, saddened by the article, resigns as the host of the show, stating that she will be pursuing a career in research.

The investor reveals that she is Evans's mother and found them due to Madeline's having sent a letter to her foundation thanking her for funding the orphanage.

Stephanie Merritt of The Guardian praised the author's ability in creating a "richly comic novel around a character who is entirely deadpan" and called the book "a polished, funny, thought-provoking story, wearing its research lightly but confidently, and with sentences so stylishly turned it’s hard to believe it’s a debut" but holding a few flaws common in debut novels, including an unfocused narrative perspective.

[19] Michael Byers from Cascadia Daily News wrote that the "heroine is brave, original and completely unafraid" and that the reasons for the book's success are clear.

Bailey opined that the final plot twist was rushed and the character writing seemed monotone, concluding with "Lessons in Chemistry is ultimately a work of fantasy.