It happened around 6:30 Sunday morning near the intersection of Aramingo Avenue and Wakeling Street.
Arriving crews were met with heavy flames coming from a one-story building.
The fire started in a vacant building but has spread to an occupied business and two adjacent homes.
Several homes on Wakeling Street have been evacuated.
SEPTA has suspended its trains on the Trenton line and Amtrak suspended its Northeast Corridor service in the area.
No injuries have been reported.
Fire crews remain on the scene battling the blaze.