Democrat Hillary Clinton and Republican Donald Trump, the national front-runners, were favored to win their respective primaries in the state that both call home.
Victories would be a tonic for both of them following a series of losses. In recent weeks, US Senator Bernie Sanders of Vermont has outclassed Clinton in nominating contests. On the Republican side, US Senator Ted Cruz of Texas, Trump's closest challenger, has outmaneuvered the billionaire businessman in the fight for delegates to the Republican National Convention that will pick the party's nominee.
By the end of Monday - the last official day of campaigning before voting in the primaries begins - tens of thousands of New Yorkers will have heard the candidates' closing pitches.
At St. John's Riverside Hospital in Yonkers just north of New York City, Clinton spoke to doctors, nurses and others at a hospital cafeteria, asking for their votes and taking a jab at Cruz's dismissal earlier in the campaign of "New York values."
"I think New York's values are America's values," she told the crowd.
New York's primaries are expected to be the most decisive in decades in the selection of the Republican and Democratic candidates for November's general election.
The question for Trump is whether he will make a clean sweep of all 95 Republican delegates at stake by earning the majority of votes in all 27 congressional districts in the state.
Total victory in New York would help the real estate magnate avoid the prospect of seeing the nomination wrested from him at the party's July 18-21 convention in Cleveland if he arrives without a clear majority of at least 1,237 delegates. In that scenario, another candidate could win on a second or subsequent ballot.
Trump has 744 delegates to 559 for Cruz and 144 for Ohio Governor John Kasich, according to the Associated Press. That count includes endorsements from several delegates who are free to support the candidate of their choice.
New York's contest comes after Cruz was awarded all 14 delegates in Wyoming's nominating contest, the latest state-by-state delegate battle, according to a party official on Saturday.
"Lyin' Ted Cruz can't win with the voters so he has to sell himself to the bosses-I am millions of VOTES ahead! Hillary would destroy him & K," Trump tweeted on Monday, also referring to Kasich.
Cruz, speaking on ABC's "Good Morning America" in Times Square, responded to Trump by saying his rival was throwing a fit because he has lost several recent state contests.
"The stakes are too high to hand the election to Hillary Clinton, which is what nominating Donald Trump (would do)," he told ABC.
Cruz also defended his "New York values" remark, which he had used in an attack on Trump months ago. He said on Monday that New Yorkers had "suffered under the left-wing Democratic policies" of New York City Mayor Bill de Blasio and Governor Andrew Cuomo.
While Cruz campaigned in New York City, Trump was to hold a rally in Buffalo, Cruz will campaign in New York City. Kasich will be in Syracuse and Schenectady, two upstate New York cities.
Sanders needs to defy expectations with a strong victory in the state if he is to overtake Clinton. In New York, 291 convention delegates are at stake.
Clinton, who needs 2,383 delegates to win the Democratic nomination, has 1,758 to Sanders' 1,076, according to AP. That total includes unpledged superdelegates who are free to back the candidates of their choice but told the news service whom they support.
Clinton, a US senator from New York for eight years, initially held a 30-percentage-point lead in opinion polls over Sanders, a Brooklyn native. But Sanders has cut that advantage by about two-thirds after an unbroken string of victories in the last eight state nominating contests.
On Monday, Sanders acknowledged that polls still showed him behind Clinton but told NBC's "Today" program: "Let's look at the real poll tomorrow."
Sanders drew about 28,000 people to Brooklyn's Prospect Park on Sunday, according to his campaign. He is hoping for more crowds at a concert and rally at a park alongside the East River in the New York City borough of Queens on Monday evening.
In addition to Yonkers, Clinton will campaign in Manhattan on Monday. Her husband, former president Bill Clinton, will head upstate to Buffalo and Rochester.
