LaPorte County Sheriff's deputies were dispatched to the scene of the crash at 6:19 a.m. in the 8600-block of East U.S. 20 near the town of New Carlisle.
Investigators said a silver Ford Taurus was travelling east on U.S. 20 and crossed the centerline, causing the left front of the car to strike the left front of a westbound semi tractor-trailer.
It is unclear why the Ford crossed the centerline of the two-lane highway, investigators said.
Both occupants of the Ford were extracted from the car by New Carlisle firefighters, which officials said took about 20 minutes to complete, and transported to Memorial Hospital in South Bend, Ind.
The 18 and 19-year-old teenagers were wearing seatbelts at the time of the accident, which investigators said saved their lives.