The flames broke out at the 2 1/2-story home on Hazel Street, near West 7th Street, around 4:30 a.m.
Firefighters arrived to find heavy flames on all three floors, and the upper floor and roof suffered heavy damage.
Two residents were injured, but both are expected to survive. They were treated for smoke inhalation at St. Joseph's Medical Center.
In total, 10 members of two families were evacuated by responding firefighters.
The cause of the fire is under investigation.
CLICK HERE for images from the scene.
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