One of the patients sustained critical injuries and was trapped in the car wreckage for nearly an hour, said ER24 spokesman Pieter Rossouw.
Rescue workers had to use the jaws of life to free the person from the wreckage before airlifting the patient to the Chris Hani Baragwanath Hospital for further treatment.
Two others sustained moderate injuries.
Police were on scene investigating the cause of the accident.
Rob Byrne tweeted:
More to follow.