It becomes an expressway near Chatfield Reservoir and the southern Denver suburbs of Littleton and Englewood, where it is commonly known as Santa Fe Drive.

They travel concurrently for three miles (4.8 km) until exit 12 when US 85 becomes an expressway and continues north out of the Denver area through Brighton.

From there it parallels I-25 for about 75 miles (121 km) passing through Fort Lupton, Platteville, Evans, Greeley, and Eaton before crossing into Wyoming.

[3] Starting in 1942, a realignment project took place in northeastern Denver, involving the opening of Vasquez Boulevard.

Originally, US 85 ran along Brighton Boulevard from downtown going northeast and then was realigned along 46th Avenue to Vasquez Bouleard.