The incident took place on the Belfast Road, Saintfield, at about 17:55 BST on Thursday, and involved a Mini, Mercedes and Mitsubishi Outlander.
The main road between Carryduff and Saintfield remains closed, and police are appealing for witnesses.
Officers want to hear from anyone who may have been driving on the A7 Belfast Road at the time and saw any of the cars.
Anyone with information is asked to contact police on the non-emergency number 101.
A woman has died in a three-car crash in County Down.