The meeting of the world's top leaders and diplomats, scheduled to begin on Tuesday, will bring street closures, thousands of police officers and hundreds of protesters to midtown Manhattan, an area already plagued with gridlock on an average weekday.
"It's the equivalent of the Super Bowl of security," said J Peter Donald, a spokesman for the New York City Police Department.
The event also comes just days after a homemade bomb on a packed commuter train in London injured 22 people, though it failed to fully explode.
Other protesters will gather outside the UN to call out specific countries, including a rally against Iran President Hassan Rouhani.
The NYPD's elite counterterrorism unit, along with detectives from the intelligence bureau and officers from the aviation, harbour, highway and traffic units, will be on hand throughout the week. Donald said the department has plenty of "muscle memory" from previous years.
The US Secret Service, the FBI, the Department of Homeland Security and various other federal agencies are also involved in providing security during both Trump's visit and the general assembly.
Vast swaths of the area near the United Nations, on the far east side of midtown Manhattan, will be closed to vehicle traffic, and the Coast Guard will heavily restrict boat traffic on the East River.
Police did not immediately offer an estimate on how much the week's security and traffic measures would cost.