The National Transportation Safety Board was expected to meet Wednesday with the California Highway Patrol amid growing evidence that the group was being smuggled into the country.
Seats of the 1997 Ford Expedition were removed, making room for more people. The SUV, which would typically seat eight to nine people legally, collided with an empty tractor-trailer on Highway 115 at Norrish Road in Holtville -- located about 125 miles east of San Diego and about 15 miles north of the Mexico border.
The area became a major route for illegal border crossings in the late 1990s after heightened enforcement in San Diego pushed migrants to more remote areas.
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U.S. Immigration and Customs Enforcement confirmed its agents were on scene to investigate if human smuggling was involved.
"Special Agents from Homeland Security Investigations San Diego responded to the scene of today's fatal crash in El Centro, California, and have initiated a human smuggling investigation," the agency said. "The investigation is ongoing and no further details are available at this time."
The Border Patrol on Wednesday said that the thirteen people killed were among more than 40 migrants who entered the country through a hole cut into Southern California's fence with Mexico.
Surveillance video showed a Ford Expedition and Chevrolet Suburban drive through the opening early Tuesday, Gregory Bovino, the Border Patrol's El Centro sector chief, told The Associated Press. It is believed they were part of a migrant smuggling operation.
The Suburban carried 19 people, and it caught fire for unknown reasons on a nearby interstate after entering the U.S. All escaped the vehicle and were taken into custody by Border Patrol agents.
The Expedition crammed with 25 people continued on, and a tractor-trailer struck it a short time later.
The Mexican government issued a statement saying that the consulate has confirmed that at least 10 of the deceased were Mexican nationals and authorities were still working to confirm the identities of the other three who were killed in the crash.
CHP officials say at the intersection the SUV drove "directly in the path of the big rig" around 6:15 a.m. The 2011 Peterbilt truck struck the left side of the SUV, which appeared to have been pushed off the road. Investigators were trying to determine if the SUV first stopped at the stop sign before entering the intersection.
Authorities said the ages of those who were inside the vehicle, including those injured and killed, ranged from 15 to 53. Numerous people were ejected onto the roadway as a result of the collision, according to officials. Initial reports said there were young children in the SUV, but officials later said the youngest occupant was 15.
The driver of the SUV, who was among those killed, was described as a man from Mexicali. Information about the occupants of the SUV, including where they were traveling to and from and why there were so many in one vehicle, is still under investigation.
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The Associated Press contributed to this report.