Police say the four were heading south on Mount Wilson Road in South Londonderry Township in Lebanon County when their car slid sideways and was hit by an oncoming vehicle late Sunday morning.
Three of the teens were pronounced dead at the scene. The teenage driver died at Penn State Milton S. Hershey Medical Center.
The driver and a passenger from the other vehicle were listed in stable condition at the hospital.
The Manheim Central School District identified the teens as freshman DeVaughn Lee, sophomores Nicolas Bryson and Cody Hollinger and junior John Griffith.
School is closed Monday for Martin Luther King Jr. Day, but counseling services will be available.
Police are investigating the crash.