The river is navigable for approximately five months of the year. It freezes over in October and the ice on the river breaks up in May. During the winter months, sections of the river are used as an ice road.
During the ice-free period the river is navigable over its entire length. Barge traffic from an intermodal hub at the railhead at Hay River serves much of the Western Arctic.
The Mackenzie (previously Disappointment River) was named after Alexander Mackenzie, who travelled the river while trying to reach the Pacific Ocean in 1789. In the Dene languages it is called Deh Cho.
The divide between the Mackenzie basin and the basin of the Yukon River to the west forms the central portion of the boundary between Northwest Territories and the Yukon.
In 2008, Canadian and Japanese researchers extracted a constant stream of natural gas from a test project at the Mallik methane hydrate field in the Mackenzie delta. This was the second such drilling at Mallik: the first took place in 2002 and used heat to release methane. In the 2008 experiment, researchers were able to extract gas by lowering the pressure, without heating, requiring significantly less energy. The Mallik gas hydrate field was first discovered by Imperial Oil in 1971-1972.