In Wyoming, the range sits west of Laramie, in Albany and Carbon counties to the route of the Union Pacific Railroad and U.S. Interstate 80.

Beginning about 70 million years ago, the Rockies began uplifting along thrust faults that broke up the Precambrian granite of Earth's crust.

The Cheyenne belt, the 1.78–1.74 billion year old suture between the Wyoming craton and the Yavapai province that formed as North America was assembled, is exposed in the Medicine Bow Mountains.

A disjunct population of arctic fairy shrimp (Brachinecta paludosa) has been documented in a few lakes in the northern part of the range.

[12] Areas of scientific inquiry at the site include atmospheric pollutant deposition, forest carbon and water vapor cycling, effect of insect outbreaks, and alpine lake and stream hydrology.