William Houston is believed to be closely related to Ann Houston (?-?) wife of John Walker III (1705-c1776) of the Wigton Walker line. Ann was the daughter of Christopher Houston (c1676-c1726) who settled in Mill Creek Hundred. He had two sons, Samuel Houston (c1699-c1740) and Robert Houston (?-?), but only Robert had children. Two of his sons are identified in Christopher's will, Christopher and James, both of whom would have had to have been born prior to 1726 when Christopher of Mill Creek Hundred died. Little is known of these children, but it is conceivable that William was one of their sons, making him a grand nephew of Ann. it is also possible that Christopher of Mill Creek Hundred had a brother or cousin, from whom William is descended, but at this time there is no evidence to support that.