Two of the drivers were pronounced dead at the scene by McMullen County Judge James Teal.
A third driver, whose rig rolled over, was extricated from the tractor rig after about 45 minutes as emergency personnel used the Jaws of Life to free him.
The 18-wheelers were carrying gravel and water from drilling.
The driver, who survived, was transported by an Airlife helicopter to University Hospital in San Antonio with life-threatening injuries, according to a medic at the scene.
Department of Public Safety troopers were investigating the accident. But how it happened was not immediately known.
Names of the deceased and sole survivor also were not known.
State Highway 72 was expected to be closed until 5:30 p.m. so the 18-wheelers could be hauled off and the roadway cleared.
Also at the scene were the McMullen EMS, McMullen Volunteer Fire Department, McMullen County Sheriff’s Office, Live Oak County Sheriff’s Office, Live Oak County Volunteer Fire Department and Acadian ambulance service.