There are officially three business routes of US 81 designated by the Texas Department of Transportation (TxDOT).

Loop 353 is the former routing of US 81 in southern San Antonio, formed in 1961 when US 81 was rerouted onto the I-35 freeway to the east.

Loop 368 is the former routing of US 81 in northern San Antonio, formed in 1962 when US 81 was rerouted onto the I-35 freeway to the east.

[6] Although not officially designated as Business US 287, the route is cosigned as such from the US 81/US 287 bypass and at the junction with FM 1655.

Blakeley carries Oklahoma State Highway 17, which has its eastern terminus at Business US-81.

The business route continues north on Rush Street before angling to the northwest to rejoin mainline US-81.

At K-61, it exits east in a 2 miles (3.2 km) "wrong-way" concurrency with K-61 before ending at I-135 and US-81 southeast of McPherson.

It shared a 4 miles (6.4 km) concurrency with K-4, which turns to the west in south Lindsborg.