The bodies of 50 people believed to be migrants were found inside an abandoned tractor-trailer rig on a remote back road in south-west San Antonio, Texas.
At least 16 others, including children, were taken to local hospitals alive, but suffered injuries including heat exhaustion, heat stroke, and dehydration.
It marks one of the deadliest tragedies in recent years among thousands of people who die attempting to cross the Mexico-U.S. border.
Mexico’s foreign minister Marcelo Ebrard said the dead included 22 Mexicans, seven Guatemalans and two Hondurans. Others have not yet been identified.
A cause of death has not officially been identified, but it is being suggested by officials that extreme heat most likely contributed. The temperature reached 101 degrees in San Antonio that day, and the truck did not have any operation air-conditioning.
The survivors were “hot to the touch” when they reached the hospital.
Border crossings have become extremely dangerous, with hundreds of migrants packed into vehicles, sometimes without any water, fresh air or food. Many have died in crashes, and many have died from overheating.
Human traffickers often use trucks to transport undocumented migrants into the United States.
It is expected that the Department of Homeland Security will take over the investigation.
The deaths come as state officials brace for a new surge in illegal crossings. Federal officials recorded a record number of crossings of the southern border for this point in the year.
Immigration campaigners and experts drew direct links between the tragedy and the U.S. border policies.
The number of people migrating globally has steadily risen over the past two decades as violence, war, climate change and poverty have led people to flee their homes.
“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.”