Investigators said the accident happened shortly after 9:00 p.m.
Police said one of the vehicles crossed the median and collided head-on with the other vehicle, triggering a fire.
U.S. 27 was shutdown in both directions and was expected to remain closed for several hours, according to investigators.
Motorists were asked to use Main Street in Nicholasville for a detour.
Look for updates online and on ABC 36 News.