Fort Yukon was built in 1847 where the Porcupine River meets the Yukon River by Alexander Hunt Murphy, a Hudson's Bay Company trader. At that time, the Fort was located within Russian territory. When the United States purchased Alaska (for a mere $7 million US) 20 years later, the HBC, fearing an armed conflict with Americans, moved their operations east (see Rampart House).

The mission hospital at Fort Yukon was the creation of Archdeacon Hudson Stuck a colourful author, missionary and explorer who was on the first expedition to climb Alaska's Mount McKinley, the highest mountain on the continent. Stuck died in 1920; when Mary arrived at the mission, the hospital was run by Stuck's prot�g� Dr. Grafton Burke. As Mary later wrote to a Lancaster newspaper, Burke's mentor "must have had a wonderful personality. It is several years since he is gone, but you'd think he was still with us - his spirit just seems to fill the north country."

Like the HBC post that would be relocated and named Rampart House, Fort Yukon was a Gwitchin community, and most of the residents were aboriginal. The international border imposed by the American and Canadian governments meant little to the Gwitchin at first, and the two communities continued to have close cultural and economic ties.