At least 30 vehicles were involved in the accident and 20 ambulances were dispatched to the scene, The Detroit News reported.
The accident in southwestern Detroit occurred during what motorists described as whiteout conditions. Emergency crews declared a HAZMAT level 3, an area extremely hazardous to health due to the possibility of spilled fuel, the newspaper said.
Michigan State Police officer Mike Shaw confirmed two of the deaths and numerous injuries, including broken limbs and back sprains.
The chain-reaction collisions on southbound I-75 caused three tractor-trailer trucks to jackknife and at least one truck to drop its load, the Detroit Free Press reported.
The Department of Homeland Security, Michigan State Police and the Detroit Fire Department participated in rescue and cleanup operations. Authorities said the highway was expected to reopen by late afternoon.
The names of dead were not released.