Leighton's prints mostly portray life and work on farms and logging camps, reflecting her love for the land and respect for the people working it. She also had a long and prolific career as a book illustrator of texts by Thomas Hardy, Emily Brontë, and Thornton Wilder, among many others, as well as fifteen books of her own.
Leighton emigrated to the United States in 1939, and after extended stays in Baltimore and North Carolina, she settled in Woodbury, Connecticut in 1951. In this later part of her career, she also created designs for Steuben Glass, Wedgewood plates, and several stained glass windows for churches in New England. She is still best known, however, for her prints, which are in the collections of the British Museum and the Victoria and Albert Museum in London, the Metropolitan Museum of Art in New York, the Art Institute of Chicago, and many more public collections in the U.S. and Europe.