Charles Sumpter, 67, and Fleitte Newell, 44, have been charged with multiple counts of murder and related offenses, according to police.
Police responded to a house fire in the 2500 block of N. Corlies Street around 4:50 a.m. on June 13.
When officials arrived, they said the home was fully engulfed in flames.
Five people were found inside the home as firefighters worked to extinguish the blaze.
Two children, 6-year-old Assad Thompson and 4-year-old Alaya Thompson-Newell, were taken to a local hospital, where they later died.
Thirty-two-year-old Ashley Thompson, who is the mother of the two deceased children and who was eight months pregnant, was pronounced dead at the scene.
Officials said a 54-year-old woman jumped from the 2nd-story window while holding her 2-year-old great-niece. Both the woman and child were hospitalized in stable condition.
Officials give update on fatal fire in Philadelphia's Strawberry Mansion section
Sources say one of the suspects is related to one of the young victims, and the motive may have been a battle over an inheritance.
On the day of the arson, police interviewed both suspects, but it was Wednesday when they served a warrant in the 2800 block of West Albert Street and made arrests.
"It was a tragedy man, them kids didn't have to die, and that pregnant lady didn't have to die," said Ronald Parker of Strawberry Mansion.