About 400 homes near the CSX tracks were evacuated early Wednesday with sleepy residents hustled off to relatives' homes, motels and Willard High School, which was closed for Thanksgiving but reopened to take in evacuees.
City officials advised residents via Twitter the evacuation order could remain in effect well into Thursday.
"Willard Public Safety and CSX clean-up crews are on the scene, but the situation is very dangerous, and the cleanup will take a while," the advisory said.
WEWS-TV, Cleveland, said the derailment shortly before midnight Tuesday left a hole in a tank car carrying 30,000 gallons of styrene monomer, an industrial chemical that is highly flammable. A half-mile radius around the Willard Rail Yard was evacuated as a precaution against a potential explosion.