A man has been brought back to life after up to 40 minutes trapped in a car submerged in a river.

The car, which was towing a boat, went off General Holmes Drive and plunged into Cooks River at Kyeemagh, in southern Sydney, about 1:15pm (AEST).

A NSW Ambulance spokeswoman said a 40-year-old man was pulled from the car by police divers after it had been submerged for up to 40 minutes.

The man was taken to St George Hospital in a critical condition after he was resuscitated at the scene, she said.

Police said the man was rescued just after 2 p.m.

A witness said the man was trapped as the car became completely submerged in the river, just south of Sydney airport.

"He couldn't get out," the woman said on Macquarie radio.

"He was trying to get out, yelling to people. There was a man that went to swim to try and help him ... but by the time he got to him the car had sunk because it had filled up with water."

Police said there were unconfirmed reports two people had been in the car and a search was continuing for the possible second person.