Francis was born in Oklahoma City, Oklahoma Territory (present-day Oklahoma) in 1905. Her parents, Joseph Sprague Gibbs and his actress wife Katharine Clinton Francis, had been married in 1903; however, by the time their daughter was four, Joseph had left the family. Francis inherited her unusual height from her father, who stood 6 feet 4 inches. She was to become Hollywood's tallest leading lady (5 ft 9 in) in the 1930s.

By that time, major film studios, which had formerly been based in New York, were already well-established in California, and many Broadway actors had been enticed to travel west to Hollywood to make sound films, including Ann Harding, Aline MacMahon, Helen Twelvetrees, Barbara Stanwyck, Humphrey Bogart, and Leslie Howard. Francis, signed to a contract with Paramount Pictures, also made the move and created an immediate impression. She frequently co-starred with William Powell and appeared in as many as six to eight movies a year, making a total of 21 films between 1929 and 1931.  Francis's career flourished in spite of a slight but distinctive speech impediment (she pronounced the letters "r" and "l" as "w") that gave rise to the nickname "Wavishing Kay Fwancis."  Francis' career at Paramount changed gears when Warner Bros. promised her star status at a better salary. She appeared in George Cukor's Girls About Town (1931) and Twenty-Four Hours (1931). After Francis' career skyrocketed at Warner Bros., she would return to Paramount for Ernst Lubitsch's Trouble in Paradise (1932).  In 1932, Warner Bros. persuaded both Francis and Powell to join the ranks of Warners stars, along with Ruth Chatterton. In exchange, Francis was given roles that allowed her a more sympathetic screen persona than had hitherto been the case--in her first three featured roles she had played a villainess. For example, in The False Madonna (1932), she played a jaded society woman nursing a terminally ill child who learns to appreciate the importance of hearth and home. On December 16, 1931, Francis and her co-stars opened the Paramount Theatre in Oakland, California with a gala preview screening of The False Madonna.

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