A pickup driver lost control on wet pavement and struck a tractor-trailer rig hauling tires about 10 p.m., Oklahoma Highway Patrol trooper Mark Reynolds said.
The pickup slammed into the tractor-trailer rig and the pickup overturned, Reynolds said.
Sparks and friction ignited the trailer and tires inside. The fire caused large plumes of smoke that slowed west bound traffic.
Fire continued to rage about an hour as I-40 was closed in both directions.
Oklahoma City firefighters battled the flames inside the shredded trailer.
Officials were still trying to determine the exact number of people involved in the wreck late Monday.
The victims' names were not immediately released.
Bystanders had stopped and pulled people from the burning wreckage.
One person was taken to a hospital in critical condition.
