The river originates west of the Mackenzie Mountains and flows 530 km (329 mi) long through the south central Yukon.

They are neighboured on the east by the Mackenzie Mountains and on their northwest end by the Brooks Range.

It rises in the Mackenzie Mountains and the community of Ross River can be found where it joins the Pelly.

Draining a rugged and high area of the Mackenzie Mountains, the Redstone watershed is sparsely populated; in fact, there are no significant settlements within the basin.

Part of the Mackenzie Mountains, it was first climbed by Bill Buckingham and Lew Surdam in July 1965.

Its ragged eastern boundary mostly follows the divide between the Yukon River Basin and the Mackenzie River watershed to the east in the Mackenzie mountains.

North of the Liard River, the Mackenzie Mountains, which are a distinct mountain range, form a portion of the border between the Yukon and the Northwest Territories.

The Canol Heritage Trail is a 355 km trail running from Norman Wells, Northwest Territories, through the Mackenzie Mountains, to the Yukon border.

The second highest peak in the Mackenzie Mountains, it is named after Major-General Sir James Howden MacBrien who was the head of the Canadian Militia in the mid-1920s.

The Muskwa and Hart Ranges together comprise what is known as the Northern Rockies (the Mackenzie Mountains north of the Liard River are sometimes referred to as being part of the Rockies but this is an unofficial designation).

'Graham County' is the name of three counties in the United States: 'Nahanni National Park Reserve' in the Dehcho Region of the Northwest Territories, Canada, approximately west of Yellowknife, protects a portion of the Mackenzie Mountains Natural Region.

Ultimately, construction proceeded both from "Canol Camp" (across the Mackenzie River from Norman Wells) and Whitehorse, and the roadway was joined in the vicinity of the Macmillan Pass in the Mackenzie Mountains, on the Yukon-Northwest Territories border, in the winter of 1942-1943.