The range forms a generally east-west arc with its most northerly part in the center, and from there trending southwest towards the Alaska Peninsula and the Aleutians, and trending southeast into the Coast Ranges. The mountains act as a high barrier to the flow of moist air from the Gulf of Alaska northwards, and thus has some of the worst weather in the world. The heavy snowfall also contributes to a number of large glaciers.
Part of the range is protected within Denali National Park. The George Parks Highway from Anchorage to Fairbanks, and the Richardson Highway from Valdez to Fairbanks pass through low parts of the range.