The crowd of black, white and Latino youths held placards saying “stop police murder,” “black lives matter” and calling for justice for African American men shot dead by US officers in recent months.
The rally began in Union Square and was organized by the Stop Mass Incarceration Network, which campaigns to end what it calls police brutality and racially biased police practices.
Protesters later marched along Broadway, disrupting traffic, and poured onto lanes of Brooklyn Bridge normally reserved for cars.
Some protesters were arrested but it was unclear how many, spokeswoman for the organizers Debra Sweet told AFP.
Police refused to comment.
The rally organizers say US police have shot more than 90 unarmed people since January. Parallel rallies were called in some two dozen other cities, including Los Angeles and Chicago, they said.
On Monday, a white volunteer deputy sheriff in Oklahoma was charged with second-degree manslaughter for shooting dead Eric Harris, 44, a suspect in an undercover gun-sale operation.
Last week, a South Carolina police officer was charged with murder after being filmed on video killing Walter Scott, an apparently unarmed black man, after a routine traffic stop on April 4.
The cellphone video shows the officer firing eight times as Scott was running away.
A series of killings last year of unarmed black men by largely white police officers sparked nationwide protests, charges of racism and revived the debate about excessive use of police force.
The demonstrations were galvanized by the August 2014 killing of 18-year-old Michael Brown in Ferguson, Missouri in bitterly disputed circumstances. The officer involved was not charged.
