Authorities say five people were aboard the helicopter. Rescue crews pulled the pilot and three others from the water, but one woman remained missing.
Following a massive rescue effort, the body of a woman was pulled from the murky waters. Her name has not been released.
Two women were taken to local hospitals with serious injuries.
The Bell 206 helicopter was submerged in the murky water, police spokesman Paul Browne said.
It's unclear what caused the private chopper to go into the river in midtown Manhattan. The weather was clear but a little windy, with winds of 10 mph gusting to 20 mph and visibility of 10 miles, according to the weather station at LaGuardia airport. There were a few clouds at 3,500 feet above sea level, well above the typical flying altitude for helicopters.
The Associated Press contributed to this report.