New York Police Chief Keechant Sewell told reporters the young woman was returning from her high school in the Bronx, accompanied by another 16-year-old girl and a boy aged 17.
A man on foot in a crosswalk was arguing with someone on the opposite side of the street when he pulled out a gun and fired repeatedly, according to Sewell.
The first teenager was hit in the chest and the other two in the leg and buttocks. All three were taken to hospital, but the most seriously injured, who should have had "a bright future", succumbed to her injuries, said the head of the NYPD.
There have been no arrests but police have CCTV footage and have promised that those responsible will be brought to justice.
It was the second time in a week that young people in New York have fallen victim to stray bullets.
On March 31, a 12-year-old boy was killed in Brooklyn while he was eating in a parked car. A 20-year-old woman was also injured in the same car.
New York's new Democratic mayor, Eric Adams, a former police officer, was elected in late 2021 on a pledge to tackle crime and the spread of illegal guns in the city of nine million people, where crime has risen sharply since the Covid-19 pandemic in 2020.
In the first quarter of 2022 the number of shootings in New York increased from 260 to 296 compared to the same period of 2021, according to NYPD figures released on Wednesday.