The dead man has been identified as Prem Suppogu, 41, of Montgomery Village in Rockville, Elkton Police said.
Elkton Police tried to pull over the vehicle, a 2008 Honda, for moving at a "high rate" of speed at 2 a.m. on Route 40 at Delaware Avenue, but the driver failed to stop, Lt. Joe Zurolo, of the Elkton Police Department, said.
The Honda kept traveling west on Route 40 and was pursued by Elkton Police, assisted by Maryland State Police and the Cecil County Sheriff's Office, according to a later news release from State Police.
Just prior to Jackson Station Road, east of Perryville, the Honda ran into the rear of a loaded tractor trailer that was also traveling west on Route 40, State Police said.
Zurolo said no one else was injured.
State Police said they are investigating the accident, while Elkton Police are investigating the circumstances leading up to the accident.