Born and raised in southern Missouri, Johnstone was the youngest of four children. His father was a minister and his mother a school teacher. He quit school when he was fifteen and worked in a carnival and as a deputy sheriff. He later served in the Army and, upon returning to civilian life, worked in radio broadcasting for 16 years.
Johnstone started his writing career in 1970, but did not have any works published until 1979 (The Devil's Kiss) and became a full-time writer in 1980. He wrote close to two hundred books in numerous genres, including suspense and horror. His main publication series were Mountain Man, The First Mountain Man, Ashes and Eagles and his own personal favorite novel was The Last of the Dog Team (1980). He also authored two novels under the pseudonym William Mason.
Johnstone had lived for many years in Shreveport, Louisiana, yet died in Knoxville, TN, at the age of 65. His death remained officially unconfirmed for nearly three years and was the subject of continuous debate in the forum on his web site. No statements were issued, however until the 2006 paperback release of Last Gunfighter: Devil's Legion, which, on its copyright page has, indeed, confirmed that "William W. Johnstone died" and that a "carefully selected author" has been chosen to carry on his legacy. J. A. Johnstone is continuing William W. Johnstone's series.