The accident happened on the R75 in Uitenhage at 6.40pm on Sunday, said Netcare 911 spokesman Chris Botha.
He said that when paramedics arrived at the scene, both lanes of the roadway were obstructed by accident debris.
Some of the injured were still trapped in the vehicles, said Botha.
Paramedics found two people had died at the scene, three were critically injured, and five had sustained serious injuries.
One of the critically injured died soon after arriving at hospital.
Botha said the injured were taken to various hospitals in the area.