William Wirt Sikes was born in Watertown, New York, the son of William Johnson Sikes, a prominent local physician.
At the age of nineteen, on August 28, 1855, he married Jeannette Annie Wilcox (1837-1889); they had two children, George Preston Sikes (1856-1957) and Clara Jeanette Sikes (1858-1956).