More than 280 people in Brooklyn and Queens have come down with measles since September.
"It's crucial for people to understand the measles vaccine works", de Blasio continued.
"The vaccine has been proven safe and effective in preventing the spread of measles for decades and we have evidence".
The health commissioner said that "nearly all" measles cases in New York City have been associated with the Orthodox Jewish community in Brooklyn, and the outbreak is the largest since 1991. Barbot said that 21 people have been hospitalized, and five have ended up in the intensive care unit.
The vast majority of cases are children under 18 years of age (246 cases), and 39 cases are adults. City health officials said Monday that yeshivas in Williamsburg, Brooklyn, that do not comply will face fines and possible closure. Extreme cases show 1 in 1,000 people suffering brain swelling, which could lead to brain damage.More news: Democratic presidential candidate Beto O'Rourke calls Israel's Benjamin Netanyahu a "racist"
Last week, a state judge blocked an attempt by Rockland County officials to halt the spread of measles by banning unvaccinated children from public places.
There have been 285 cases of measles since the outbreak began in the fall, mostly in the ultra-Orthodox Jewish community, and the number has more than doubled since February.
"This outbreak is being fueled by a small group of anti-vaxxers in these neighbourhoods". They have been spreading unsafe misinformation based on fake science.
Tuesday's announcement was the first time NY has ordered mandatory vaccinations in recent history, according to health officials. "But as a doctor, a public health practitioner, and a mom, I must warn you that exposing your unvaccinated child to measles is very unsafe, and it could even be deadly".
"We stand with the majority of people in this community who have worked hard to protect their children and those at risk". According to the Centers for Disease Control and Prevention, 465 measles cases have been reported so far this year, up from 387 the week before.More news: WWE: Becky Lynch beats Ronda Rousey at Wrestlemania
The mandate orders all unvaccinated people in four Zip codes, including a concentration of Orthodox Jews, to receive inoculations, including for children as young as 6 months old. "I urge everyone to get vaccinated". It says the vaccine is 97 percent effective.
His deputy mayor for Health and Human Services, Dr. Herminia Palacio, also warned about the risk to others, and mentioned "measles parties" where parents purposely take their uninfected kids to be near infected children.
The announcement comes a day after DOH threatened to close Williamsburg yeshivas that allow unvaccinated students to attend school in light of the epidemic.
The CDC recommends that all children get two doses of measles vaccine.More news: Brexit: UK asks European Union for further extension until June 30