Beginning at a junction with US 60 at Pampa in Gray County, SH 273 runs south to a junction with Loop 171. In Pampa the highway is known as Cuyler Street and Barnes Street. After a brief co-routing with Loop 171, the highway runs southeast to Lefors and then south to a junction with Interstate 40 at McLean, where the route is known as Sitter Street. SH 273 then runs almost directly south to its final junction with SH 203 near Hedley in Donley County. Most of the terrain covered by the highway is lightly populated ranch and oil country.