Wyoming Highway 220 begins its western end in Carbon County at US 287/WYO 789 at Muddy Gap Junction and from there heads northeast toward Casper.

[2] WYO 220 passes north of the reservoir, now traveling more easterly as it comes upon the census-designated place (CDP) of Alcova, the center of population of Wyoming.

Past Alcova, WYO 220 turns back northeast and begins to parallel the North Platte River and continue until it reaches Casper.

[2] WYO 220 originally terminated at US 20 and US 26 in downtown Casper and was later extended north along Center Street to I-25, which was completed in October 1960.

[5] The first phase of the project, a new bridge over the North Platte River and the Chicago, Burlington and Quincy Railroad, opened in late 1968.