Tan and her mother did not speak for six months after Tan dropped out of the Baptist college her mother had selected for her, Linfield College in Oregon, to follow her boyfriend to San Jose City College in California. Tan met him on a blind date and married him in 1974. Tan later received bachelor’s and master’s degrees in English and linguistics from San Jose State University. She took doctoral courses in linguistics at University of California, Santa Cruz and University of California, Berkeley.

Daisy subsequently moved Amy and her younger brother, John Jr., to Switzerland, where Amy finished high school at the Institut Monte Rosa, Montreux. During this period, Amy learned about her mother’s previous marriage to another man in China, of their four children (a son who died as a toddler and three daughters), and how her mother left these children behind in Shanghai. This incident was the basis for Tan’s first novel The Joy Luck Club. In 1987, Amy traveled with Daisy to China. There, Amy met her three half-sisters.

Tan began writing her first novel, The Joy Luck Club while working as a business writer, and joined a writers’ workshop, the Squaw Valley Program, to refine her draft. She submitted a part of the draft novel as a story titled ‘Endgame’ to the workshop. Author Molly Giles, who was teaching at the workshop, encouraged Tan to send some of her writing to magazines, and stories by her, drawn from the manuscript of the Joy Luck Club were published by both, FM Magazine and Seventeen, although a story was rejected by the New Yorker. Working with agent Sandra Dijkstra, Tan published several other parts of the novel as short stories, before it was sent as a draft novel manuscript. She received offers from several major publishing houses, including A.A. Knopf, Vintage, Harper & Row, Weidenfeld & Nicolson, Simon and Schuster, and Putnam Books, but declined them all as they offered compensation that she and agent considered to be insufficient. She eventually accepted a second offer from Putnam Books, for $50000 in December 1987. The Joy Luck Club, consists of eight related stories about the experiences of four Chinese–American mother–daughter pairs.

Tan’s work has been adapted into several different forms of media. The Joy Luck Club was adapted into a play in 1993; that same year, director Wayne Wang adapted the book into a film. The Bonesetter’s Daughter was adapted into an opera in 2008. Tan’s children’s book, Sagwa, the Chinese Siamese Cat was adapted into an PBS animated television show, also named Sagwa, the Chinese Siamese Cat.

In 1998, Tan contracted Lyme disease, which went misdiagnosed for a few years. As a result, she suffers complications like epileptic seizures. Tan co-founded LymeAid 4 Kids, which helps uninsured children pay for treatment. She wrote about her life with Lyme disease in The New York Times.

Tan had a difficult relationship with her mother. At one point, Daisy held a knife to her throat and threatened to kill her while the two were arguing over Amy’s new boyfriend. Her mother wanted Tan to be independent, stressing that Tan needed to make sure she was self-sufficient. Tan later found out that her mother had three abortions while in China. Daisy often threatened to kill herself, saying that she wanted to join her mother (Tan’s grandmother, who also committed suicide). She attempted suicide but never succeeded. Daisy died in 1999.