Multiple media outlets reported the fire started at the old Seneca Baptist Church around 11 p.m. Saturday. Six fire departments responded to the blaze.
Seneca firefighter Chris Cartee says the roof caved in the middle of the church and the left side of the building and attic suffered significant damage.
The building housed the church from 1925 to 2005.
Cartee says the State Law Enforcement Division and the federal Bureau of Alcohol, Tobacco and Firearms are investigating the cause of the fire.
Seneca Mayor Dan Alexander says a Spanish-speaking church from Walhalla had bought the building and had been remodeling it for months.