Police responded after a suspect drove onto a busy bicycle path and struck several people, then emerged from the vehicle screaming and firing something that appeared to be a gun.
Officers were called to the incident a few blocks from the World Trade Center site and memorial.
Officials are treating the attack as a terrorist incident.
A law enforcement official says at least six people were killed and at least 15 people were struck by a rented van.
The New York Police Department posted on its Twitter feed that one person was in custody.
A large number of police vehicles could be seen in Manhattan near West Street and Chambers Street, which is near a community college and a high school and a few blocks north of the National Sept. 11 Memorial.
The New York Police Department later posted on Twitter: “A vehicle entered the West Street pedestrian/bike path a few blocks north of Chambers Street.
“The vehicle struck multiple people on the path. There are several fatalities and numerous people injured.
“The vehicle continued south, striking another vehicle. The suspect exited the vehicle displaying imitation firearms and was shot by NYPD. The suspect is in custody.”