Bill was born on January 21, 1940 in Taft, a small town in south Texas. After his parents divorced, he and his brother moved with their mother to Gregory, where she ran a small telephone office during WWII. He later used these experiences as a basis for his feature film, Raggedy Man.

Shortly after graduating from the University of Texas, he and his wife, Sally, started their own book publishing company, The Encino Press. It specialized in regional material about Texas and the Southwest and operated out of a 19th-century Victorian house in Austin in which O. Henry once lived and wrote. The Encino Press won over 100 awards for quality of design and content.

Wittliff was also an accomplished photographer, whose photographs documenting the life of the Mexican vaquero, have been exhibited throughout the United States and Mexico. This collection was sent to Japan to represent the United States in its bicentennial year.

In 1985, the Wittliffs founded the Southwestern Writers Collection at Southwest Texas State University with the donation of their collection or original manuscripts and books. The collection has continued to grow with the support of donors all over the world. The collection also contains paintings by regional artists. In 1996, the Wittliffs endowed the Wittliff Gallery of Southwestern & Mexican Photography to the university. Both collections are housed on the top floor of the Albert B. Alkek Library on the university campus.