The teenager who was killed was seated near the back of the bus when it was rear-ended around 9 a.m. at a railroad crossing south of Michigan Road on northbound US-31 in Marshall County.
After the train crossing gate opened and the bus began to accelerate, the semi-truck struck, which was towing a trailer, struck the left rear side of the bus, according to Indiana State Police.
The name of the teenager who died had not been released as of Tuesday afternoon.
Police said a 14-year-old was airlifted from the crash scene to Memorial Hospital in South Bend, Ind. with non life-threatening injuries. Several other students were taken to Saint Joseph Regional Medial Center in Plymouth, Ind. Their conditions were unknown.
The driver of the truck was identified as Perry Taylor, 26, of Camby, Ind. The bus driver is Cheryl Warner, 54, of Winamac, Ind. Police said Warner had been legally stopped at the train train tracks prior to the crash.
Three adult chaperones were also on the bus. Police did not say whether any of the adults were injured.
Toxicology results are pending for both drivers, and no charges have been filed.
Northbound US 31 is closed while authorities investigate the crash scene.