U.S. Highway 181 is a south–north U.S. Highway located entirely in the state of Texas. Both termini are at Interstate 37, the road that it mainly parallels to the east. US 181 begins in Corpus Christi, Texas at mile marker 0 to the south, through south-central Texas to just south of San Antonio to the north, for a total length of 137 miles (220 km).

Interstate 37 (I-37) is a 143-mile (230 km) Interstate Highway located within the southern portion of the US state of Texas. The highway was first designated in 1959 as a route between Corpus Christi and San Antonio. Construction in the urban areas of Corpus Christi and San Antonio began in the 1960s, and the segments of the Interstate Highway in rural areas were completed by the 1980s. Prior to I-37, the route between Corpus Christi and San Antonio was served by a combination of State Highway 9 (SH 9) from Corpus Christi to Three Rivers and US Highway 281 (US 281) from Three Rivers to San Antonio. As a result of the construction of I-37, SH 9 was removed from the State Highway System.