The highway travels just east of the city's downtown area through a large commercial area, with development along the route decreasing north of SH 351 near Hardin-Simmons University.

The Treadaway Boulevard designation ends at Pine Street, with Bus.

North of Hardin-Simmons, the highway's route becomes more rural with some industrial areas and has an interchange with I-20 southeast of Impact.

US 83-D turns northwest near Huckleberry Road and travels through rural areas of the city before ending at an interchange with US 83 / US 277 near FM 3034.

The highway travels in a western direction along Washington Avenue, briefly runs in a northern direction along Trevino Street, then turns east onto Uribe Street.

US 83-N turns north onto Morelos Street, then turns northeast onto Santa Maria Avenue before ending at an intersection with US 83 near the San Ygnacio Community Center.

US 83-S) is a business loop of US 83 in the Lower Rio Grande Valley region.

The highway serves as the main street for many communities in the area, such as McAllen, Mission, San Juan, Alamo, and more.