Born in Kansas City, Missouri to William Q. and Cecile "Frankie" Franking Wu, William F. Wu attended the University of Michigan (U-M) where he received an AB degree in East Asian Studies and, later, an AM and then PhD in American Culture in 1979 with his doctoral dissertation, "The Yellow Peril: Chinese Americans in American Fiction, 1850-1940," a version of which would later be published in 1982 by Archon Books. During this time, Wu was actively involved in East Wind, an Asian American student organization at U-M.

While pursuing graduate studies at U-M, Wu also made his first professional sale as a writer in 1975. He became a member of the Science Fiction Writers of America (SFWA) in 1977 and later a member of the SFWA Bulletin staff in 1981.

In the years following, Wu wrote and published 15 novels, including MasterPlay (1987), Isaac Asimov's Robot City #3: Cyborg (1987), Isaac Asimov's Robot City #6: Perihelion (1988), Dr. Bones and the Cosmic Bomber (1989), Hong on the Range (1989), Robert Silverberg's Time Tours #1: Robin Hood Ambush (1990), the Isaac Asimov's Robots in Time series (1993-1994), Mutant Chronicles, Vol. 1: In Lunacy (1993), Realms of Chaos: An Enemy Reborn (1998) with Michael A. Stackpole, and A Temple of Forgotten Spirits: The Complete Series of Jack Hong (2018).

Wu also wrote and published, in collaboration and individually, over 70 works of short fiction featured in presses and publications such as Amazing Stories, Analog Science Fact/Science Fiction, Isaac Asimov's Science Fiction Magazine, Eldritch Tales, Omni, and Pulphouse: The Hardback Magazine. Wu also contributed short stories to the Wild Cards series edited by George R. R. Martin and Melinda M. Snodgrass. Two of Wu's short works, "Wong's Lost and Found Emporium" and "Hong's Bluff," were nominated for a Nebula Award in 1983 and 1985 and a Hugo Award in 1984 and 1986, respectively. "Wong's Lost and Found Emporium" was also nominated for a World Fantasy Award in 1984 and was later adapted into a Twilight Zone episode in 1985.

Wu contributed a number of nonfiction works and commentary to various publications and small presses with a particular focus on topics of Asian American and Chinese identity and representation in popular culture and American fiction, science fiction works and authors, and history and life in the Palmdale, California area.

In 1997, Wu became a copy editor at the Antelope Valley Press in Palmdale, California and received a number of promotions over the years before leaving the newspaper in 2017.