No one lives permanently at York Factory; there is a summer residence for Parks Canada staff, and some nearby seasonal hunting camps.

[3] From the 17th to the late 19th century, the depot at York Factory and its predecessors were the central base of operations for the Hudson's Bay Company's (HBC) control of the fur trade and other business dealings with the First Nations throughout Rupert's Land, the vast territory comprising the entire watershed of Hudson Bay, and which now forms much of Canada.

During King William's War, France several times sent a naval force to Hudson Bay to capture or destroy the fort.

In response, the company began sending out its own traders from the depot and eventually established inland posts, first along the Saskatchewan River, and then stretching as far as the Oregon Country.

Twice annually from 1821 to 1846, brigades known as the York Factory Express travelled overland to Fort Vancouver headquarters for the HBC's Columbia Department, brought supplies and trade goods, and returned with furs destined for London.

By the mid-19th century, York Factory had developed an extensive trading post and settlement with 50 on-site buildings, most of which have been destroyed, and a permanent workforce.

The chief trader, John McLean, wrote that he "took leave of Fort York, its fogs, and bogs and mosquitoes, with little regret" in 1837.

The transfer of Rupert's Land to Canada and the changes in the HBC Northwest transportation network increased the use of the United States railways, steamboats, and Red River carts for Upper Fort Garry's southern supply line.

In 1873, the post's fur trade headquarters title was removed, and certain responsibilities were transferred to Upper Fort Garry, present-day Winnipeg.

The residents were relocated to York Landing Cree Nation,[7] about 116 kilometres (72 miles) ENE of Thompson, Manitoba, as well as Split Lake and Shamattawa.

In oral stories, Cree elders who once resided at York Factory in the first half of the twentieth century recalled their desires to remain at Kihci-waskahikan or Great House when operations ceased.