Lloyd Zachary was born in Boston, the son of Daniel and Elizabeth Zachary. Orphaned as a child, he moved to Philadelphia to live with Mr. Hills, his uncle. Here he studied medicine with Dr. John Kearsley. After years of travel in Europe, Zachary began his practice of medicine in Philadelphia in 1726. He served as health officer for the port of Philadelphia from 1729 until 1741.
He was a founder and trustee of the College and Academy of Philadelphia (now the University of Pennsylvania), and Pennsylvania Hospital. He was deeply devoted to the latter institution, serving as one of the original medical staff until he was paralyzed by a stroke in 1753; at the time of his death in 1756 he left £350 and his personal library to Pennsylvania Hospital.