SR 133 begins at an intersection with US 84/US 221/SR 38/SR 94 (West Hill Avenue) in Valdosta, within Lowndes County.

It has an interchange with Interstate 75 (I-75) before passing through Troupville and crossing over the Withlacoochee and Little rivers, the latter one marksing the Lowndes–Brooks county line.

The road passes through the town of Berlin, and past the Spence Airport, before it reaches Moultrie.

A short distance later, SR 37 departs to the northeast The concurrency curves to the northwest to meet the northern terminus of US 319 Business.

The highways split, and SR 133 travels through rural areas of the county until it reaches Doerun.

At North Broad Street, the highways split, with SR 133 continuing to head west.

Finally, it continues northwest for a little while until it meets its northern terminus, an intersection with US 19/SR 3 (Walnut Street), north of Albany.

is a 6.1-mile-long (9.8 km) alternate route that exists entirely within the central part of Colquitt County.