Set in Glendale, California, in the 1930s, the book is the story of middle-class housewife Mildred Pierce's attempts to maintain her family's social position during the Great Depression.
Mildred separates from her unemployed husband and sets out to support herself and her children. After a difficult search she finds a job as a waitress, but she worries that it is beneath her middle-class station. More than that, she worries that her ambitious and increasingly pretentious elder daughter, Veda, will think her new job demeaning. Mildred encounters both success and failure as she opens three successful restaurants, operates a pie-selling business and copes with the death of her younger daughter, Ray. Veda enjoys her mother's newfound financial success but increasingly turns ungrateful, demanding more and more from her hard-working mother while openly condemning her and anyone who must work for a living.
When Mildred discovers her daughter's plot to blackmail a wealthy family with a fake pregnancy, she kicks her out of their house. Veda, who has been training to become an opera singer, goes on to a great deal of fame as Mildred convinces her new boyfriend Monty (a young man who, like Mildred, lost his family's wealth at the start of the Great Depression) to help reconcile them. Unfortunately for Mildred, this means buying Monty's family estate and using her earnings to pay for Veda's extravagances. Mildred and Monty marry, but things go sour for her: Wally, her partner in the restaurant business, has discovered that her living like a rich person has dramatically affected the company's profits. He threatens a coup to force her out of the company. This causes her to confess to her ex-husband Bert that she has been embezzling money from her company in order to buy Veda's love.
Needing some of Veda's money to balance the books – and fearing that Wally might target the girl's assets if they are exposed – Mildred goes to her house to confront her. She finds Veda in bed with her stepfather. Monty explains to Mildred that he's leaving her for Veda, who gloats that they have been planning this all along. Mildred snaps, brutally attacking and apparently strangling her daughter, who now appears incapable of singing and loses her singing contract.
Weeks pass as Mildred moves to Reno, Nevada, to establish residency in order to get a speedy divorce from Monty. Bert moves out to visit her. Mildred ultimately is forced to resign from her business empire, leaving it to Ida, a former company assistant. Bert and Mildred, upon the finalization of her divorce, remarry. They are shocked when Veda shows up with several dozen reporters to "reconcile" with her mother (a move designed to defuse the negative publicity of her sleeping with her stepfather). Mildred accepts, but several months later, Veda reveals that her voice has healed and announces that she is moving to New York City with Monty. Veda's apparent loss of her voice was only a ploy so that she could renege on her existing singing contract and then be free to establish a more lucrative singing contract with another company. As she leaves the house, a broken Mildred agrees to say "to hell" with the monstrous Veda and to "get stinko" (drunk) with Bert.