The mountains act as a high barrier to the flow of moist air from the Gulf of Alaska northwards, and thus have some of the harshest weather in the world.

The range is part of the Pacific Ring of Fire, and the Denali Fault that runs along its southern edge is responsible for many major earthquakes.

Mount Spurr is a stratovolcano located at the northeastern end of the Aleutian Volcanic Arc which has two vents, the summit and nearby Crater Peak.

A part of the Alaska Highway is situated on the northern slopes of the eastern section of the range.

In 1898, W. C. Mendenhall and E. F. Glenn traversed Isabel Pass and were within 15–20 miles of the Tanana River before turning around.