A male and a female died in the shooting at a back yard event, interim police chief Mark Simmons told reporters.
None of the 14 wounded people taken to hospital suffered life-threatening injuries, Mr Simmons said.
Speaking from the scene, the police chief said: "This is truly a tragedy of epic proportions."
The shooting comes after the city's police department was rocked by the suffocation death of Daniel Prude.
Video taken in March and made public by Mr Prude's family on September 4 shows him handcuffed and naked with a spit hood over his head as an officer pushes his face against the street while another officer presses a knee to his back.
The officers held him down for about two minutes until he stopped breathing. He was taken off life support a week later.
On Monday, Rochester mayor Lovely Warren sacked police chief La'Ron Singletary, who she said initially misled her about the circumstances of Mr Prude's death.
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