Fisher was born Mary Frances Kennedy in Albion, Michigan, on July 3, 1908. In 1911, her father, Rex Kennedy, moved the family to Whittier, California, to pursue a career in journalism. Although Whittier was primarily a Quaker community at that time, Mary Frances was brought up within the Episcopal Church.

While studying at the University of California in 1929, Fisher met her first husband, Alfred Young Fisher. The couple spent the first formative years of their marriage in Europe, primarily at the University of Dijon in France. At the time, Dijon was known as one of the major culinary centers of the world and this certainly had an impact on Fisher, who later went on to become one of the great culinary writers of the twentieth century. These three years in Dijon are recounted in her later book "Long ago in France."

In 1932, the couple returned from France to a country ravaged by the Great Depression. Having lived for years as students on a fixed stipend, they were wholly unprepared for the economic situation that faced them. Al got odd jobs cleaning out houses before finally landing a teaching job at Occidental College in Los Angeles. Fisher did her part teaching a few lessons at an all-girls school and working in a frame shop.

In addition to being an author, Fisher was an amateur sculptor working mostly in the realm of wood carving.

During the Fishers' years in California, they formed a friendship with Dillwyn "Timmy" Parrish and his wife, Gigi. Later, in 1938, Fisher was to leave Alfred for Timmy, referred to as "Chexbres" in many of her books, named after the small Swiss village on Lake Geneva close to where they had lived. The second marriage, while passionate, was short. Only a year into the marriage, Parrish lost his leg due to a circulatory disease, and in 1941 took his own life. Fisher went on to be involved in a number of other turbulent romantic relationships with men and women.

Fisher bore two daughters. Anna, whose father Fisher refused to name, was born in 1943. Mary Kennedy was born in 1946, during Fisher's marriage to Donald Friede, which lasted from 1945 to 1951.

After Parrish's death, Fisher considered herself a "ghost" of a person, but went on to live a long and productive life, dying in California in 1992 at the age of 83. She had long suffered from Parkinson's disease and arthritis, but lived the last twenty years of her life in "Last House," a house built for her in one of California's vineyards.

A full list of her works can be found at The MFK Fisher Foundation Webpage.