The flames broke out on Main Street in Huntington around 3 a.m., burning through a two-story structure used by at least four businesses.
Firefighters arrived to find heavy smoke billowing out of the building, and half a dozen departments were called in from surrounding towns to help.
A nearby apartment building was evacuated as a precaution.
The fire was brought under control within a few hours, and there are no reports of injuries.
The stretch of Main Street near Woodbury Road remains closed.