Federal Aviation Administration spokesperson Kathleen Bergen said flight 5191 crashed at 6:07am after taking off from the Lexington airport on its flight to Atlanta.
The regional jet had 47 passengers and three crew members aboard.
One survivor is being treated at University of Kentucky hospital. UK spokesperson Jay Blanton said no other survivors have been brought to the hospital.
Comair Presdient Don Bornhorst identified the Captain as Jeffrey Clay, a 7 year veteran of the company. He was hired in December of 1999 and became a captain in 2004. Other members of the flight crew were identified as first officer Jim Polehinki, hired in 2002, and flight attendant Kelly Heyer.
The plane involved was CRJ 50 seat commuter aircraft.
N-T-S-B and FAA investigators are headed to the scene. Two "black boxes" that were aboard the aircraft have been found. The boxes contain flight information for the plane.
There's no immediate word on what caused the crash in the filed about a mile from the Blue Grass airport.
A dedicated toll-free number has been established for family members of customers on flight 5191 at 1-800-801-0088.