Born in Washington, DC in the late nineteenth century, Fisher grew up in Providence, Rhode Island graduating from Classical High School and attending Brown University. He earned his Bachelor of Arts from Brown in 1919, where he delivered the valedictory address, and received a Master of Arts a year later. He went on to attend Howard University Medical School and graduated in 1924. He held a fellowship at Columbia University School of Medicine, during which time he published two scientific articles of his research on treating bacteriophage viruses with ultraviolet light. Fisher married Jane Ryder in 1925, and they had one son, Hugh, who was born in 1926. Fisher died after unsuccessful abdominal surgery in 1934 at the age of 37.

• City of Refuge (1925)
• High Yaller
• The Walls of Jericho (1928), about black life in Harlem
• The Conjure-Man Dies (1932)

City of Refuge and another short story, Vestiges, were included in Alain Locke's anthology, The New Negro.

In 1991, an anthology of Fisher's short fiction, City of Refuge: The Collected Stories of Rudolph Fisher, was published by the University of Missouri Press.