Loop 281 begins at a partial cloverleaf interchange with I-20/US 259/SH 322 in southern Longview; the highway continues south past I-20/US 259 as SH 322.

Loop 281 briefly dips in a southwestern direction before turning back northwest, traveling near many industrial areas in south/southwest Longview.

Loop 281 starts to travel in a northeast direction at FM 1845 (Pine Tree Toad), passing by a few residential areas.

The highway passes a few blocks north of Longview Regional Medical Center then has an interchange with US 259 (Eastman Road); from here, the route of Loop 281 gradually becomes more rural with little development.

Development along the route slightly picks up near County Road 3413, with Loop 281 passing by a rural subdivision with some business lining the highway.