The crash happened Thursday just before 11 p.m. near 12th and Meridian streets in downtown Indianapolis.
Police say the person driving a green Oldsmobile Delta 88 turned in front of the motorcycle driver.
According to witnesses, the motorcyclist was forced to lay his bike down and slid into the rear of the car.
He was taken to a local hospital in critical condition, but he died overnight.
Police are asking for the public's help to find who was driving the car.
If you have any information, call Crime Stoppers at 317-262-TIPS.