William Guest was born in Frederick County, Virginia on December 30, 1762. A resident of Wilkes County, North Carolina, in June 1777 he enlisted in the county militia and guarded Fort Defiance on the Yadkin River for a term of about three months. Later in March 1779 he enlisted as a private under his brother Captain Moses Guest's command in the Wilkes County Light Horse Regiment of the North Carolina Militia. He married Anna Allen in Wilkes County, North Carolina on July 29, 1779. During this tour of service William Guest went out to Watagua, a settlement in present-day Tennessee and to Long Island of the Holston in present-day Kingsport, Tennessee. He also spent time looking for roving bands of Tories in western North Carolina. Guest later saw combat at the Battle of Ramsours Mill in June 1780 and at the Battle of Kings Mountain in October 1780. After King's Mountain, he marched British and loyalist prisoners to present-day Winston-Salem. Col. Benjamin Cleveland then sent Guest to retrieve his wounded messmate, Joseph Reid, and bring him from Burke County to Wilkes County. After completing that task, he rejoined his unit on the Catawba River, where he received his discharge in October 1781.

William and Anna Guest had at least six children together and they moved to Pickens District, South Carolina in 1785, where they resided for the rest of their lives. In 1833 Guest applied for a pension on account of his wartime service and received one in 1834 in observance of his two years of service as a private, worth $80 per year from 1831 until the time of his death. His claim was readjusted in 1838, granting him $50 per year. He died in Pickens District, South Carolina on July 8, 1841.