The McGills were metalworkers and, from 1715 onward, burgesses of the city and members of the Hammermen's Guild, James' father having served as deacon.

He entered the fur trade south of the Great Lakes, at first as a clerk or agent for the Quebec merchant, William Grant of St.

[5] In 1775, McGill (along with Todd, Benjamin, and Joseph Frobisher, and Maurice-Regis Blondeau) sent 12 canoes to a port in Grand Portage (near modern Grand Portage, Minnesota) - this shipment in particular proves important for Canadian history as it (according to historian Harold Adams Innis) "appeared to mark the beginning of large-scale trade to the Northwest (of Canada)...and of the Northwest Company".

The partnership did not participate in the North West Company after 1783, but it continued in the so-called "Southwest trade" in the Mississippi valley until Michilimackinac was handed over to the Americans in 1796.

In November 1775, McGill was a member of the representation for the citizens of Montreal at the drafting of the articles of capitulation for the city to the invading American army.

He was the first honorary lieutenant-colonel of the 1st Battalion, Montreal Militia, a unit which later evolved into the Canadian Grenadier Guards, as commemorated by the replicated cairn that stands before the Arts building of McGill University.

In 1782, McGill would be responsible with making the largest investment in Lower Canada within the fur trade in history at that time, some 26,000 Pound Sterling.

Educated at the Ursuline Convent, Quebec, she was the daughter of Guillaume Guillimin (1713-1750), Member of the Sovereign Council of New France and Judge of the Courts of Admiralty.

McGill had previously adopted Charlotte, the youngest daughter of his deceased friend John Porteous, and through his marriage (after the death of their uncle and legal guardian) he became the step-father of two sons, In 1777, at Montreal, McGill purchased the former home of the Baron de Becancourt for his new family on Notre-Dame Street, next to the Château Ramezay.

The high sloping roof had dormer windows for the third floor rooms, of which only two (each measuring twenty four square feet) had ceilings, while the rest of the area was a large open attic.

McGill's major assets included real estate in Lower and Upper Canada and investments in Britain; the latter not specified as to character or amount.

James McGill was buried, alongside his fur-trading associate John Porteous, in the old Protestant "Dufferin Square Cemetery".