It travels for 643 miles (1,035 km) from Liberal, Kansas at US 54 and US 83 to White Hall, Arkansas at Interstate 530 (I-530) and US 65.

After leaving the Panhandle and picking up US 183 near Fort Supply, the highways turn southwest towards Woodward.

Major interchanges with I-44 and I-35 (the latter involving a concurrency with the interstate and its accompanying US Highway, US 62) are found in the city.

US 270 serves most of the towns anchoring the area east of Oklahoma City, including Shawnee, Tecumseh, Seminole, Wewoka, and Holdenville.

It also serves many of the small towns east of McAlester, such as Krebs, Alderson, Bache, Haileyville, and Hartshorne.

After passing through Hartshorne, the roads curves to the northeast before turning onto a due east course taking it through Wilburton, Red Oak, and Wister.

The town highways head south from Heavener, passing through the Wister Wildlife Management Area before entering the Ouachita National Forest.

The route trails east towards Pine Bluff terminating at and interchanging with I-530/US 65 in White Hall.

[1] The roadway was mostly gravel or graded earth, with some segments in the Ouachita Mountains still under construction upon designation.

[2] In 1935, the US 270 designation supplanted the remainder of State Road 6 between Hot Springs and US 65 west of Pine Bluff.

This request was denied by the American Association of State Highway Officials in an October 14, 1967 meeting.

[7] In a November 14, 1980 resolution, the American Association of State Highway and Transportation Officials approved a request by KDOT to truncate US-270 to its current terminus in Liberal.

[citation needed] U.S. Highway 270B is a 8.90-mile-long (14.32 km) business route in Garland County, Arkansas.