Norfolk Southern said it appeared about 11 cars of a southbound train derailed around 2 a.m. near Interstate 71, southeast of the Ohio State University campus. They went off the tracks north of downtown, in an industrial area blocks from residential neighborhoods.
It wasn't immediately clear what caused the crash, how many cars caught fire or what they contained. Authorities believe the cargo included some type of alcohol that could fuel the fire, said Battalion Chief Michael Fowler, a spokesman for the Columbus fire division.
One of the cars was also carrying Styrene, a chemical used in making plastics, but officials said that car wasn't punctured, reports CBS affiliate WBNS-TV.
Hazmat officials on the scene said there was no risk for air contamination, according to WBNS.
Two people who ran toward the scene before the explosion were injured but were able to take themselves to a hospital, Fowler said.
Norfolk Southern said none of its workers were hurt.
Photographer Chris Mumma said he was more than 10 miles away in New Albany when he saw the night sky brightened by a "huge illumination" that he later learned was an explosion. He said he went to the scene to take photos and saw punctures on top of the train that were spewing flames 20 to 30 feet high. He also noticed an odd odor.
"I noticed there was a chemical smell, and I was inhaling it so I backed up a little bit more because I wasn't sure what I was getting involved with," he said. Mumma said it made him so nauseous that he ended up at the hospital.
Fowler said a site at the state fairgrounds was set up to help about 100 evacuees.
As daylight broke, Fowler said authorities would have a better picture of the fire scene to determine whether they'd try to extinguish the blaze or simply let it burn out.
Norfolk Southern said two locomotives and three of the train's 98 freight cars were safely removed from the scene.