The crash happened in the eastbound lanes of I-80 in Ottawa, about 80 miles southwest of Chicago in LaSalle County.
The bus was from LaSalle Peru High School and was traveling to Morris for a basketball tournament.
Fire officials say 16 people were on board. The bus driver and two students were taken to a hospital to be treated for their injuries.
The fire chief says its fortunate the bus did not roll over. Still, a team coach described it as "very scary."
"They were screaming a little bit," said Coach Jason Miller. "But I think everyone was just trying to hang on. My assistant and i we just yelled to hang on and try to stay low. And that's what they did because everyone came out okay."
"Investigators don't know what caused the bus to leave the road and there is no word on the injuries."