The dead man was identified as Jacob Matthew Huber, 24, of Ruffs Dale, Westmoreland County. He was wearing a seatbelt at the time of the crash.
WTAE-TV reported that the driver of the other vehicle and a passenger, both of whom are from Ohio, were flown to the hospital with injuries. Their condition was unknown on Tuesday.
Pennsylvania State Police did not know why the vehicle was traveling northbound in the the southbound lane.
The incident remains under investigation.