William Wirt Sikes was born in Watertown, New York, the son of William Johnson Sikes, a prominent local physician. He was the seventh of eleven children, of whom only six survived to adulthood. Sikes himself was seriously ill as a child and almost lost his hearing, so he was largely educated at home. At fourteen he went to work for a printer and learned how to set type. He supported himself thereafter by typesetting, contributing to local newspapers, and giving temperance lectures.
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).