State Highway 72 (SH 72) is a Texas state highway that runs approximately 111 miles (179 km) from near Fowlerton to Cuero in South Texas.

SH 72 begins in far western McMullen County, near the La Salle County line, at an intersection with SH 97 north of Fowlerton. The highway has no major intersections until it intersects SH 16 north of Tilden. The two routes run concurrently into Tilden, where SH 72 resumes its eastward path, passing south of Choke Canyon Reservoir and State Park before entering Live Oak County. The highway enters Three Rivers, where it intersects and runs concurrently with US 281 through the city center. After separating from US 281, SH 72 takes a more northeasterly trajectory for the remainder of its journey. After crossing I-37 at the freeway's exit #69, it continues through rural Live Oak County and briefly passes through Bee County before entering Karnes County. In Kenedy, SH 72 intersects US 181 and passes through the city's downtown along Main Street; SH 72's only business route is also in this city. To the east of the city, SH 72 intersects SH 239 and passes through Runge before entering DeWitt County. The highway passes through Yorktown along that city's Main Street, intersecting SH 119. SH 72 intersects US 87 to the west of Cuero before it turns to the east and into the city. SH 72 ends at US 77 Alt. / US 87 / US 183 on the south side of Cuero.

SH 72 was originally proposed in 1926 from Kenedy to Carmine, absorbing previously designated SH 3B. By 1939, its route had been readjusted, with the section north of Cuero transferred to US 77 and SH 237, and a section added from Kenedy to Cotulla. In 1942, the section from Cotulla to Three Rivers was either cancelled or transferred to SH 97 and Farm to Market Road 63. In 1961, the section from Fowlerton to Three Rivers was transferred back to SH 72. The section from the junction with US 87 west of Cuero into the city was designated Farm to Market Road 3402 beginning in 1983; this section was combined with SH 72 in 1994, completing the current route.

SH 72 has seen increased traffic due to oil and gas exploration of the Eagle Ford Formation; recent counts have indicated that traffic on SH 72 exceeds that on US 87 around Cuero. As a result, TxDOT is considering the addition of shoulders to SH 72 in western DeWitt County.

SH 72 has one business route, Business SH 72-B in Kenedy, which is a former alignment of the state highway along Karnes Street through that city. The route was designated as Spur 542 in 1982, when SH 72 was rerouted to use Main Street. The western end of the business route is at US 181 Bus., which was renumbered from Spur 259 the same year.