One of the four victims slain in the gun violence was a 36-year-old New York Police Department officer who immigrated to the US from Bangladesh.
Mayor Eric Adams described the officer, who had been on the force for more than three years, as a "true blue" hero.
Authorities offered few details about the three other victims killed by the suspect - two men and a woman.
A third male was gravely wounded by the gunfire and was "fighting for his life" in a nearby hospital, the mayor said.
New York Police Commissioner Jessica Tisch said the gunman, identified as Shane Tamura, 27-year-old Las Vegas resident with a history of mental illness, had driven cross-country to New York in recent days.
The gunman was believed to have acted alone, and investigators had yet to determine a possible motive for the shooting, Tisch told reporters at a late-night news briefing.
"Pure evil came to the heart of our city and struck innocent people and one of our police officers who were protecting those people," Patrick Hendry, president of the Police Benevolent Association, said at the media conference.
The slain policeman, Didarul Islam, a father of two whose wife is pregnant with a third child, was working at the time as part of an NYPD program that allows its uniformed patrol officers to be assigned as security detail in commercial establishments.
The shooting spree in the evening rush hour began in the lobby of the Park Avenue tower in midtown Manhattan, then shifted to the upper-storey offices of a management company as the suspect took the elevator to the 33rd floor.
The bloodshed came to an end when the gunman fatally shot himself in the chest, Tisch told reporters.
A photo of the suspect that CNN said was shared by police showing a gunman walking into the building carrying a rifle was published by a number of major news media outlets.
Preliminary checks of the suspect's background did not show a significant criminal history, the report said, citing officials.
The skyscraper at 345 Park Avenue houses offices of a number of financial institutions, including Blackstone and KPMG, along with the headquarters of the National Football League.
A large police presence converged on the area around the tower, according to Reuters journalists near the scene.
The FBI said agents from its New York field office were also responding to provide support at the scene.
