It happened shortly after 8:30 p.m. on the 300 block of W. Mount Airy Avenue in the city's West Mount Airy neighborhood.
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Arriving crews found heavy flames showing from the first floor of a two-story residence.
Once inside, firefighters discovered 70-year-old Elaine Morris dead inside a second-floor bedroom.
They also found 7-month-old Ren Fields in a rear bedroom and rushed him to the hospital. He later died from his injuries.
Officials say a 33-year-old woman and two other children, ages 7 and 8, all escaped the fire with minor injuries.
Fire officials say a neighbor heard screams from inside when the fire broke out.
"He saw a young child in the second-floor rear of that property. He urged the child to jump. The child did jump. The neighbor caught the child. They both fell, but the neighbor broke the child's fall. That child sustained no injuries and that neighbor through his actions prevented some serious injuries," Assistant Fire Chief Harry Bannan said.
Officials say the neighbor also helped the 33-year-old woman evacuate the home and prevented her from going back inside.
A total of two adults and three children occupied the home.
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The fire was placed under control in about 20 minutes.
There was no immediate word on what sparked the fire.