The fire broke out shortly before 11 a.m. Wednesday at Klein's Motel in Muhlenberg Township, Berks County.
WFMZ-TV said one firefighter suffered minor injuries.
Firefighters said the motel office, the motel owner's living area and an adjacent storage building all sustained heavy damage. The rear of the structure partially collapsed from the fire.
Officials said high winds have hampered their efforts to extinguish the blaze.