James McGill was born in Glasgow, Scotland, in 1744. He entered Glasgow University in 1756, but did not receive a degree. He later immigrated to the American colonies and the first known North American reference to McGill dates from 1766. In about 1774, he arrived in Montréal and, in partnership with Isaac Todd, became involved in the commercial fur trade. For a time, he also maintained business partnerships with his brothers, Andrew and John. McGill was a member of the Beaver Club, a private social club based around participation in the fur trade. From 1792 to 1796, and from 1800 to 1804, he represented a Montréal constituency in the Lower Canada Legislature, and in 1793 he was appointed to the Executive Council. In 1776, McGill married Marie-Charlotte Guillimin, the widow of a former colleague, Amable Desrivières. James McGill enslaved at least six Black and Indigenous people: Sarah, Marie-Louise, Jacques, Marie-Charles, Marie, and a Chatiks si chatiks (Pawnee) child whose name is not recorded. In 1813, he bequeathed a large part of his estate to the Royal Institution for the Advancement of Learning in order to found and endow a college bearing his name. After delays and litigation by heirs, McGill College was inaugurated in 1829.

Andrew McGill was born in 1754 in Glasgow, Scotland and died in 1805 in Montreal. He was the son of James McGill and Margaret Gibson and was the brother of James McGill (founder of McGill University), John McGill, and Isobel McGill. He was married to Ann Wood and when McGill died, she married his brother James. With his brother James, McGill founded James and Andrew McGill and Company in 1810, which had succeeded Todd, McGill and Company.