The Philadelphia Fire Department described it as a "fatal fire" without giving further details, saying officials would hold a news briefing later Wednesday morning near the house in the East Coast city's Fairmount neighborhood.
Firefighters arrived around 6:40 a.m. (1140 GMT) and fought for about 50 minutes to control the fire on the second floor of the three-story house, the department said in statements on social media.
The department did not immediately comment on injuries and deaths. NBC10 News and other news outlets said at least 13 people were killed in the building, and that two other people were taken to a hospital in critical condition.
News outlets said the building was owned by the city's public housing authority.