The roof of the bus was crushed and all the windows were knocked out, with one thrown as far as 25 yards.
DPS spokesman Bart Graves said two men and four women, all aboard the bus, were killed. The bus, traveling from central Mexico to Los Angeles, was carrying at least 22 passengers, and the surviving 16 passengers were all injured. Police said the rollover triggered a second accident when another pickup slowed and was hit by a sedan. One person from the sedan was taken to a hospital.
Eight of the injured were taken to Maricopa Medical Center in Phoenix, where six were in critical condition with life-threatening injuries ranging from broken spines and pelvises to head injuries, hospital spokesman Michael Murphy said.
He said an 11-year-old boy and the bus driver were among the patients at the hospital, and that the two were in guarded condition with non-life-threatening injuries.
Four patients, two in critical condition and two in good condition, were taken to Scottsdale Healthcare Osborn hospital. Three patients, one in critical condition and two in good condition, were taken to St. Joseph's Hospital and Medical Center in Phoenix. Two others were at Banner Good Samaritan Medical Center in Phoenix, but the hospital did not release their conditions.
Early reports said the bus hit a semi, but Graves said later a semi was not involved in the crash.
Police said the bus hit the pickup, veered into the central median, then overcorrected and rolled once before landing on its wheels.
The accident scene quickly became a mass of police and rescue personnel as ambulances arrived and medics set up a triage area in the middle of the normally busy interstate, preparing the injured for transport.
Medical helicopters landed on the freeway to airlift the most critically injured to area hospitals.
The bus originated in central Mexico near Durango, Graves said. It entered the United States at El Paso, Texas, and was traveling westbound on I-10.
Two drivers were onboard, the main driver and a relief driver. The plan was to switch drivers in Phoenix, Graves said.
Graves said the investigation will include whether the driver was fatigued as well as the maintenance history of the bus.
The bus is owned by Tierra Santa Inc. A phone message left by The Associated Press was not immediately returned.
Both westbound lanes of I-10 were closed at milepost 173, and traffic was being rerouted onto State Route 587 until further notice.
The accident scene, about 25 miles south of downtown Phoenix, remained under investigation.