The highway begins at an intersection with US 83 in Carrizo Springs, about 60 miles northwest of Laredo.

On the outskirts of Randlett, this ends as U.S. 277-281 turn northward and pass under I-44 (with no interchange there) before entering Cookietown.

The route proceeds from there to serve several other towns bypassed by I-44, such as Fletcher, Cyril, and Cement, crossing the turnpike twice without direct access.

Entering the town of Chickasha with U.S. 81, U.S. 277 turns east along U.S. 62 and follows it all the way to its northern terminus at I-44 near Newcastle.

Bailey Turnpike between Oklahoma City and the Red River from Newcastle southwest of Oklahoma to near Medicine Park north of Lawton and from near Geronimo south of Lawton to Randlett just north of the Red River near Burkburnett, Texas.

The original northern terminus was in Oklahoma City at its intersection with parent route US 77 and US 62.

[citation needed] On March 15, 2022, a bill was signed by President Joe Biden that added the extension of I-27 north to Raton, New Mexico, and south to Laredo to the Interstate Highway System.

The extension would utilize the US 277 corridor between San Angelo and Carrizo Springs, Texas.

Present U.S. 281 Business and former U.S. 277-281 follows 2nd Street south of I-44 (Exit 39B) into the downtown area and south of Lee Boulevard (Oklahoma 7), curves into the diagonal route to 11th Street and still locally designated by the City of Lawton as Highway 277 even though it is officially designated as U.S. 281 Business.