A handful of people were arrested, police and witnesses said, but no violence was reported.
"Donald Trump, go away, racist, sexist, anti-gay," shouted the demonstrators who gathered at Manhattan's Columbus Circle, near one of the billionaire real estate mogul's luxury buildings overlooking Central Park.
Amid a considerable police presence, protesters held up signs that read "Deport Trump" and "Build a wall around Trump." Also spotted in the crowd were placards on which were written "Don't let bigotry Trump our constitution" and "Will trade 1 Donald Trump for 25,000 refugees."
At least one person was arrested on the city's famous Fifth Avenue during a brief skirmish that was quickly brought under control by police.
The demonstration was organized by a group called Cosmopolitan Antifascists, with others joining in.
Ordinary New Yorkers turned out for the event, concerned by Trump's status as the clear frontrunner for the Republican party's nomination ahead of November's presidential elections. Trump "is racist, he is sexist, he is homophobic, he is Islamophobic, xenophobic, he is a fascist. It has serious implication for the future of America," Patrick Waldo told AFP.
"If we start closing our borders to some people based on their religious beliefs, that is completely unconstitutional ... we start going to a World War II Germany kind of situation and I don't want that in my country," the 31-year-old historian added. Trump has called for a ban on all Muslims entering the United States, just one example of rhetoric by the candidate that has sparked controversy on the 2016 campaign trail.
"Everything he says is racist, is false. It hurts my feelings," said Nour Hapatsha, a 22-year-old Muslim born in the United States.
Some pro-Trump supporters also showed up.
"More and more, people who show their support to Donald Trump are intimidated," said one among them, Jim MacDonald. "We are here to show that it is still America for the time being ... we have a right to free speech," he added.
"As frightening as this is, we are going to show that we have the right to show our support to Donald Trump whether it pleases the other side or not."
- 'Dump Trump' -
In the southwestern state of Arizona, meanwhile, protesters blocked a major thoroughfare in an attempt to prevent Trump supporters reaching a rally he was due to hold ahead of the state's primary next Tuesday.
The estimated 50 protesters held a banner across the width of Shea Boulevard with the words "Dump Trump" as long lines of traffic backed up in Fountain Hills, on the outskirts of Phoenix.
Controversial Maricopa County Sheriff Joe Arpaio, who openly endorsed and supports Trump, said he would do everything possible to ensure the event would go ahead -- and Trump subsequently took the stage.
Deputy Joaquin Enriquez told AFP that three people were arrested and that two vehicles were towed. "These arrests were made because they were blocking a public roadway, not for protesting," he said.
Demonstrations and violence have broken out at several Trump events recently, with critics saying the businessman's inflammatory rhetoric and barely-veiled threats directed at protesters have been fueling an increasingly toxic atmosphere surrounding his rallies.