The Audi rammed into the truck from behind at about 4pm on Sunday, said Captain Mohlaka Mashiane.
The driver of the car, aged 70, was severely injured and was taken to Polokwane hospital. His three passengers, including his wife, died in the accident.
Two of the passengers were also husband and wife and in their late 60s.
Mashiane said the couple lived in the US and had been visiting Polokwane.
A case of culpable homicide had been opened.
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