William Masters was the son of Thomas Masters, mayor of Philadelphia from 1707 to 1709. He inherited “Green Spring,” a large tract of land in the Northern Liberties section of Philadelphia, where he lived and where he operated the Globe Mill. A man of considerable wealth, he married Mary Lawrence, the daughter of Councillor Thomas Lawrence. His daughter Mary married Richard Penn in 1772.
Masters was a member of the provincial assembly and a commissioner to spend money designated for the defense of the province of Pennsylvania. He was also a founder and trustee of the College and Academy of Philadelphia (now the University of Pennsylvania), serving until his death in 1760.