A bookseller from 1668, dealing largely in Bibles, Guy ultimately amassed a fortune from printing and shrewd investments. In 1704 he became a governor of St. Thomas's Hospital, Southwark, and he paid for the construction (1707) of three new wards. In the 1720s, finding St. Thomas's still overcrowded, he built Guy's Hospital across the street. He was member of Parliament for Tamworth from 1695 to 1707; he also was chosen sheriff of London but declined to serve.