State Highway 16, or SH 16, is a south-north state highway that runs from Zapata on the Texas-Mexico boundary to U.S. Highway 281 24 miles (38.6 km) south of Wichita Falls. It is the longest state highway in Texas at almost 542 miles, but is only the 9th longest highway overall in the state.

SH 16 begins at an intersection with US 281 between Windthorst and Antelope in North Texas, and begins it journey to the south. It reaches an intersection with US 380 in the town of Graham. It continues to the southeast, wrapping around the northern and eastern sides of Possum Kingdom Lake. Its next intersection is with I-20 south of the town of Strawn. It continues south through farm and ranchland in Central Texas, passing through the cities of Comanche and Llano. The route veers to the southeast as it reaches the Texas Hill Country, passing through Fredericksburg, Kerrville, and Bandera. The routes enters San Antonio from the northwest, and goes around the west side of the city concurrent with Interstate 410. The route continues to the south through San Antonio's far south side and then through south Texas ranchlands, finally reaching its final terminus at US 83 in Zapata, almost 542 miles from its starting point.

SH 16 was one of the original twenty six state highways proposed in 1917, overlayed on top of the Fort Worth-Oklahoma Highway. From 1917 the routing mostly followed present day Interstate 35W from Fort Worth to Denton. It continued on, routed along present day Interstate 35 from Fort Worth through to Oklahoma. By 1919, the route was cancelled. It was then reassigned to the future route of U.S. Highway 181 (which was routed over it in 1926) from San Antonio to Corpus Christi. It was reassigned by 1933 to a new section between Santa Anna and Brady over previous SH 4 and was rerouted over SH 51 from Crowell to Sagerton, and was being extended northward to the Oklahoma State line via Quanah. By 1936, SH 16 was extended north over part of SH 81 to Kerrville. By 1939, the section from Brady to Santa Anna was promptly reassigned to U.S. Highway 183.

SH 16 extended north to north of Graham, terminating near Buena Vista south of San Antonio, replacing SH 81. In 1965 the road was significantly extended via its current routing to Zapata, replacing State Highway 346 from San Antonio to Jourdanton, and was rerouted over Interstate 410 in San Antonio.