Emergency crews have been evacuating residents from their homes within a 1.6km radius of the fire, according to several reports.
It is not immediately clear if there are any casualties, Reuters reported.
The East Palestine police department did not immediately respond to a Reuters request for details.
Freight railroad company Norfolk Southern Corp is “coordinating closely with local first responders while mobilizing our own teams”, a company spokesperson said in an emailed statement.
The person did not immediately respond to queries about what the train was carrying or what caused the derailment.
