Harrison was born in 1880 in Sewanee, Tennessee. Caskie Harrison, his father, was a professor and doctor. In 1885, the family relocated to Brooklyn, New York, where Dr. Harrison established a Latin school. Harrison and his two siblings were well-educated. Harrison attended Columbia University, graduating in 1900 at age 20. He served as editor of the Columbia newspaper and participated in productions put on by the school’s dramatic society. After graduation, he taught and continued writing. Upon his father’s death in 1902, Harrison and his family relocated to Richmond, Virginia, where he worked for the Times-Dispatch. He became a columnist and an editorial writer who focused on politics and social issues. He began to write fiction while working on the newspaper.

Harrison resigned from the paper in 1910, relocating to Charleston, West Virginia, where he focused on writing literature. His first novel, Captivating Mary Carstairs, was published later that year. This book was followed closely by his second novel, Queed, in 1911. The seemingly semi-autobiographical book sold well and brought Harrison into the public eye. Harrison's popularity generated interest in his short story “Miss Hinch,” which was first published in McClure’s Magazine that year and later anthologized in many collections.