Frances Parkinson Wheeler split her time in childhood between Boston, Massachusetts, and the village of Newbury, Vermont. She was educated privately and traveled widely throughout Europe. In 1904, at the age of 18, she married Henry Wilder Keyes, a politician who eventually became governor and then U.S. Senator from New Hampshire, and the couple lived on his family estate near Haverhill with their three sons.
After her husband's death in 1938, Frances Parkinson Keyes settled in the French Quarter of New Orleans.
Her career as a writer began with the publication of her first novel, Old Gray Homestead, in 1919. During the 1920s, she wrote a series called "Letters from a Senator's Wife," for Good Housekeeping Magazine, where she served as a contributing editor; the columns were later collected and published in book form. Keyes also wrote about her experiences as a political wife in two memoirs, Capital Kaleidoscope: The Story of a Washington Hostess (1937) and All Flags Flying (published posthumously in 1972), as well as a novel, All That Glitters (1941).
Frances converted to Catholicism and this experience fueled much of her writing on religious subjects, both fiction and nonfiction.