Rekha Sindu was killed on the spot when the driver of the car she was travelling "dozed off" and rammed the vehicle into the median, Natrampalli police said.
The incident happened on the busy Chennai-Bengaluru highway and three other occupants of the car, including the driver, sustained injuries, police said.
The victim was on her way to Bengaluru.
Meanwhile, in an apparent case of mistaken identity, some reports claimed that another Kannada actor, Rekha Krishnappa, was the one who was killed in the mishap, prompting her to issue a clarification.
"I am all fine guys.....At present in Sringeri sharada peeta temple," she wrote on her Facebook page and also put up a video.