Mary Murfree studied at Chegaray Institute, a French school in Philadelphia, in 1867–69. With the failure of her father's business in 1869 the family returned to their native Murfreesboro, Tennessee (which was named in 1811 for her great-grandfather). There Murfree began writing stories for her own and her family's entertainment. In 1874 one of her stories appeared in Lippincott's Magazine under the name “R. Emmet Dembry,” and her writing career was begun. A story in The Atlantic Monthly in 1878 appeared under the name “Charles Egbert Craddock,” which she used thereafter.

Murfree's first book, In the Tennessee Mountains (1884), collects several of her stories from the Atlantic. Where the Battle Was Fought (1884), her first novel, was followed by In the Clouds (1886), The Despot of Broomsedge Cove (1889), In the “Stranger People's” Country (1891), His Vanished Star (1894), The Juggler (1897), and The Young Mountaineers (1897), among others. The revelation in 1885 of Charles Craddock's true identity added greatly to Murfree's celebrity and to interest in her writing. Her knowledge of mountaineer ways and rural dialect enabled her to make a large contribution to the local-colour movement in American fiction; however, her work was frequently marred by formal shortcomings in diction and development.

Murfree's later works are mostly historical fictions, and while they indicate the maturing of her craft they lack the spontaneity of her earlier work.