The Democrat has given approximately 46,000 unvaccinated city employees until November 1 to get their first vaccine dose, and he offered an incentive: city workers who a shot by October 29 at a city-run vaccination site will get an extra $US500 ($A666) in their paycheck.
"My job as your mayor is to keep this city safe, keep this city healthy. And vaccination is the way," he said.
Unions representing some city employees immediately castigated the mandates as an unfair invasion of personal privacy.
New York City's largest police union, the Police Benevolent Association, said getting vaccinated is a "personal medical decision" officers should make in consultation with their doctors.
"Now that the city has moved to unilaterally impose a mandate, we will proceed with legal action to protect our members' rights," said its president, Pat Lynch.
The city previously mandated vaccines for public school teachers and the state has previously mandated vaccines for hospital workers.
With the expanded mandate, more than 300,000 city employees will need to be vaccinated, roughly 160,000 more than had previously been covered by vaccination rules.
Jailers on Rikers Island, where the city has been grappling with staffing shortages creating unsafe conditions, won't be subject to the mandate until December 1.
De Blasio had been weighing a vaccine mandate for the police and fire departments and other city agencies for several weeks.
His announcement came amid new uproar over NYPD officers defying even simple measures, like wearing face masks.
On Monday, two police officers were seen on video shoving a man out of a Manhattan subway station when he confronted them for flouting rules requiring they wear masks.
About 69 per cent of the NYPD's workforce is vaccinated, compared with 77.4 per cent of adult New Yorkers who have been fully vaccinated.
New York City's mandate comes as other cities are starting to punish - and even fire - emergency workers who fail to meet vaccine requirements.
The state has mandated vaccines for health care workers and people in New York City must show proof of vaccination to eat indoors at restaurants or to attend sporting events - or even play in them.
One of the city's biggest basketball stars, Brooklyn Nets guard Kyrie Irving, has been banned from playing or practising for refusing to get the vaccine.
In barring the seven-time all star, the team cited New York City rules that pro athletes playing for a team in the city must be vaccinated against COVID-19 to play or practice in public venues.
