There have been no injuries reported, but officials warned that some residents may not get to go home Thursday for Thanksgiving.
The trouble began in Willard, pop. 6,180, on Tuesday night, when a rail car was damaged in a derailment and began to spill a chemical called styrene monomer, officials said.
Styrene mononor is a colorless liquid used in the manufacture of plastics that can cause some inflammation and irritation for humans who breathe and touch it, but officials are more immediately concerned that the material is highly flammable.
"If you, or someone you know, live in the affected area, please leave NOW," the city tweeted from its official account, fearing a blast around the Willard Rail Yard and prompting much of the city's northwest quarter to evacuate.
The city manager couldn't immediately be reached for comment Wednesday. Police estimated about 400 homes had to be evacuated, according to WEWS-TV.
In a statement, the railroad company, CSX Transportation, said it was working with local officials to deal with the derailment and that the leak had been stopped. CSX said it was helping place residents in hotel rooms and setting up an outreach center in the community's town hall.
However, the city tweeted Wednesday, "Due to the concerns for public safety, the cleanup efforts by CSX is going slower than originally anticipated."
Officials warned that the evacuation order would be in place until further notice and that some residents may not be able to return home for a few days.