It runs for 116.879 miles (188.1 km) between U.S. Route 160 (US 160) in Cortez and SH 141 near Naturita.

The route begins in the south at its intersection with US 160 in the eastern portion of the city of Cortez.

The route winds northward through the towns of Dolores, Rico, Sawpit, Placerville, Norwood, and Redvale before terminating at the junction with SH 141 about four miles (6.4 km) east of Naturita.

Just north of its midpoint between Rico and Sawpit, the road also passes very near and provides access to the town of Telluride as well as Trout Lake.

On May 24, 2019, a large boulder fell onto a section of SH-145 near Dolores and covered the roadway.