The accident happened Sunday morning on Interstate 70 near Richmond, which is about 70 miles east of Indianapolis and 35 miles west of Dayton, Ohio, where it planned to make a stop. Authorities temporarily closed all lanes of the highway before reopening them about three hours later.
The cause of the collision was being investigated.
Wayne County spokesman Jonathan Duke said one person was reportedly killed and 18 others were taken by ambulance or helicopter to hospitals. He didn't know the extent of the injuries.
A dispatcher with the Wayne County Sheriff's Department said she believed the driver of the bus, which sustained heavy damage to its front end, was airlifted to an Indianapolis hospital. The driver's condition was not immediately available.
About 20 injured people were taken to Reid Memorial Hospital in Richmond, including many who were treated for minor injuries such as cuts, scrapes and bruises, hospital spokesman Larry Price said. About half of them had already been discharged.
"I would describe them as walking and wounded," Price said. "At last check it didn't appear that we were going to have to admit someone."
Brandi Schroeder, who drove past the accident scene while returning home to Indianapolis from Ohio, said the bus ended up off the shoulder of the highway's eastbound lane and that the other vehicle lay crushed in the inbound lane. She said that vehicle was so badly flattened that she couldn't see its wheels or whether it had been a car or truck.
"I've seen a lot of accidents, and I've never seen anything like this," Schroeder told The Associated Press. She said there were police cars and fire trucks everywhere.
The bus, which was traveling from St. Louis to Dayton, Ohio, and ultimately to New York City, was carrying 24 passengers and the driver, Greyhound spokeswoman Alexandria Pedrini said. Two new buses were dispatched to Richmond for the passengers, she said.
Pedrini said she could not release any information on the driver.