Emergency services were called to the crash in Clutha Valley Rd, about 5km west of Balclutha, at 3.45pm.
Constable Andy Denny, of Balclutha, said the elderly male driver of a silver Toyota Camry had to be freed from his vehicle by firefighters using cutting equipment. The female driver of the second vehicle, a blue Ford Falcon, did not require assistance to get out of her car.
A spokeswoman for St John said both received moderate injuries and were taken to Clutha Health First for medical treatment.
Const Denny said he believed neither vehicle was carrying passengers, but a dog found at the scene was thought to have been in the man's car and was taken to Clutha Vets to be checked.
Clutha Valley Rd was closed for an hour.
Police are investigating the cause of the crash.
