SH 163 runs almost directly north from its originating junction with U.S. Highway 90 at Comstock near the Rio Grande, the southern border of the state.

The road passes east of the Seminole Canyon State Historical Park and along the Devils River to the ghost town of Juno.

[2] Counties traversed by the highway include Val Verde, Crockett, Irion, Tom Green, Sterling, and Mitchell.

Most of the terrain covered by the highway is sparsely populated ranch country.

The original formation of the highway on February 26, 1930 (numbered on March 19, 1930) included only the section from Ozona to Barnhart.