The two were riding with another mother and her four-month-old son when the car collided with a SUV at the Boulevard and Harbison Avenue around 11:30 p.m. Thursday.
Police said there were two car seats in the car and that the four-month-old was properly strapped into a car seat in the back, but it's unclear why the other child was not.
The one-month-old girl was pronounced dead at Einstein Medical Center.
Her 19-year-old mother is stable with bumps and bruises, investigators said.
The four-month-old boy suffered minor injuries and is listed as stable. His 21-year-old mother sustained injuries to her legs and is also stable.
The 29-year-old male driver of the SUV was taken to the hospital, but police said he was not injured.
Debris was left behind on the Boulevard and the airbags deployed in the vehicles.
Investigators said the vehicles were driving in opposite directions in different lanes on Harbison just before the crash.
"Preliminary information has these two vehicles both on Harbison Avenue, one was going eastbound, one was going westbound, and when they were crossing the Boulevard in the southbound lanes, that's when the vehicles struck each other head on," Small said.
Action News was originally told the SUV attempted to make a left-hand turn and collided with the car, but later learned from police the car was making the turn and t-boned the SUV.
Investigators are still trying to determine who had the right of way.
Small said police were questioning the adults at the hospital as well as checking surveillance video at the scene. Investigators are also looking at driving records.