SH 123 begins at an intersection with US 181 just south of Karnes City and proceeds northward along the town's eastern edge.

The road continues north through farmlands before reaching an intersection with US Route 87 in Stockdale.

Reaching Seguin, Texas State Highway 46 begins, peeling off to the northwest toward New Braunfels.

SH 123 continues around the eastern edge of Seguin, where it is known locally as "the Bypass", and there it intersects US 90 Alternate, US 90, and Interstate 10.

The highway continues north, reaching its northern terminus at Interstate 35 in San Marcos.