Paramedics rushed to the scene on the east side of Midtown Manhattan.
A fire official told NBC News that six others suffered minor injuries.
The collision, reported shortly after 4 p.m., happened at East 39th Street and Third Avenue in Manhattan during what a senior police official said was “the People March in Solidarity With ICE Detainees.”
A witness told NBC New York a BMW struck a group of demonstrators. “The woman is plowing through, I run out of the way, I see bodies flying,” she said.
Paramedics, firefighters and police officers rushed to the scene, where a scooter-based officer flagged down the driver and a passenger, police said. The two were being questioned by New York Police Department investigators.
A city official briefed on recent protests said this was one of several collisions where protesters gathered near vehicles, and drivers panicked and accidentally accelerated.