U.S. Route 50 (US 50) is a part of the U.S. Highway System that travels from West Sacramento, California, to Ocean City, Maryland. In the U.S. state of Colorado, US 50 is a major highway crossing through the lower midsection of the state. It connects the Western Slope with the lower Front Range and the Arkansas Valley. The highway serves the areas of Pueblo and Grand Junction as well as many other smaller areas along its corridor. The long-term project to widen the highway from two lanes to a four lane expressway between Grand Junction and Montrose was completed in January 2005. Only about 25% of the remainder of highway 50 in Colorado is four lane highway.

Pueblo is a home rule municipality that is the county seat and the most populous municipality of Pueblo County, Colorado, United States. The city population was 111,876 at the 2020 United States Census, making Pueblo the ninth most populous city in Colorado. Pueblo is the principal city of the Pueblo, CO Metropolitan Statistical Area and a major city of the Front Range Urban Corridor.