It happened around 8:30 p.m. inside a home on the 5500 block of Blakemore Street in the city's Germantown section.
Police say the 16-year-old girl was with two other teens when the unknown device was detonated.
The explosion was so powerful part of the floor from the second story home could be seen hanging into the living room.
"The last report we have is most of her right foot is gone," said Chief Inspector Scott Small.
The girl was rushed to an area hospital where she's currently listed in stable condition.
According to Small, the girl did not live at the home and it appears the device may have been illegal.
"Based on the bomb squad personnel's preliminary information, they say that some sort of powerful explosive device. It's not commercial fireworks, it is illegal to possess," Small said.
The injury comes just 24 hours after a device exploded in the hand of a 12-year-old boy Tuesday night.
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According to officials, the boy was immediately taken into surgery at St. Christopher's where surgeons removed the remaining part of his left hand. He is reportedly in critical but stable condition.
The Bomb Squad came to the scene to determine what exactly exploded in the boy's hand. It's not yet known exactly what type of device it was - or if it was a firework, if it was within legal limits.
"We're not really certain what type of explosive device he was handling. It appears that with the injuries to his hand and it was such a loud explosion, they believe possibly something like an M-80 or something the size of a quarter stick of dynamite in that area, we're not certain," said Small on Tuesday night.
M-80 fireworks are illegal under federal guidelines because they have more explosive power than what's allowed.