The rally marked his first on Long Island.
The former president focused on immigration as a top campaign issue and made it a key focus of his remarks Wednesday in Uniondale.
"We're just destroying the fabric of life in our country. And we're not going to take it any longer. And you got to get rid of these people. Give me a shot," Trump said.
He ripped into Democratic leadership in New York City and state, blaming them for homeless people living in what he called "horrible, disgusting, dangerous, filthy encampments," and even the conditions on the New York City subway, which he called "squalid and unsafe" and promised to renovate.
"What the hell do you have to lose?" he said in asking for their votes.
Trump has promised to carry out "the largest deportation operation in the history of our country" if he's elected in November. He has offered no details on how such an operation would work.
"Look at what's happening," he told his crowd in New York. "Businesses that are fleeing, money draining out of your state and hundreds of thousands of illegal migrants sucking your public resources dry."
The big rally came just days after the second apparent attempt on the former president's life in Florida over the weekend.
More than 60,000 tickets were requested for the big event even though the facility only seats 16,000. And while tens of thousands of his supporters couldn't get inside the venue, they stuck around just to be near the Republican presidential nominee and watched his address on large screens outside.
Trump said he plans in the next two weeks to visit Springfield, Ohio, which has been the center of false accusations from the former president and his running mate JD Vance that members of the city's Haitian community are abducting and eating cats and dogs.
In the meantime, while Trump spends time in Manhattan at Trump Tower, the Secret Service has increased security for the former president. They now have a tent for his arrivals and departures, an additional step that brings Trump even closer to presidential-level security.
56th Street between Fifth and Madison had already been closed to traffic following the Pennsylvania shooting, but now there is a vehicle barricade as you would see outside a government building blocking access.
Former president Trump is expected to stop in Brooklyn on Thursday before traveling to Washington, DC for a 6 p.m. "Fighting Anti-Semitism in America Event," followed by a speech at the American Council National Summit.
Trump has long maintained strong support in the Jewish community and is courting Democratic Jewish voters in response to increasing criticisms by progressives of the Israel-Hamas war.
The Associated Press contributed to this report.
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