The Nueces rises northwest of San Antonio in the Edwards Plateau, in Real County, roughly 50 mi (80 km) north of Uvalde.

It flows south through the Texas Hill Country, past Barksdale and Crystal City, approaching to within 35 mi (56 km) of the Rio Grande on the border with Mexico.

Called Chotilapacquen by Coahuiltecan-speaking groups, the river was named "Nueces" by Alonso de León referring to the abundant pecan tree groves.

[3] From before the end of the Texas Revolution, Mexico recognized that the Nueces River was historically the border between its states of Coahuila y Tejas and Tamaulipas.

[4] On August 10, 1862, pro-Union Germans from the Texas Hill Country trying to flee to Mexico were ambushed and killed by Confederates—the Nueces massacre.