At least 46 migrants were found dead in Texas at an abandoned lorry
A fire official said 16 people, including four children, had also been taken to hospital.
The survivors were "hot to the touch" and suffering from heat stroke and exhaustion.
San Antonio, which is 250km (150 miles) from the US-Mexican border, is a significant transit route for people smugglers.
Human traffickers often use lorries to transport undocumented migrants after meeting them in remote areas once they cross into the United States.
"They had families...and were likely trying to find a better life," San Antonio Mayor Ron Nirenberg said. "It's nothing short of a horrific, human tragedy."
Emergency responders arrived at the scene at about 18:00 local time (23:00 GMT) after responding to reports of a dead body, San Antonio fire chief Charles Hood told reporters.
"We're not supposed to open up a truck and see stacks of bodies. None of us come to work imagining that," he said.
He added that the vehicle, which its driver had abandoned, had no working air conditioning, and there was no drinking water inside it.
Mexico's Foreign Minister, Marcelo Ebrard, said that two Guatemalans were among those taken to hospital. The nationalities of the other victims were not immediately apparent.
Three people are held in custody, and the investigation has been handed over to federal agents.
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