The former vice-president had to stop speaking while he waited for the protesters to finish.
Mr Biden had been challenged on the number of deportations during the first two years of President Obama’s administration.
Told that the 800,000 people removed from the United States during that period had been higher than the number deported during the first two years of President Trump’s term, Mr Biden was asked whether the higher numbers would resume should be make it to the White House.
He replied “absolutely not” – but as he did so two women on either side of the Fox Theater shouted: “Three million deportations!”
Mr Biden, the frontrunner for the Democratic nomination, went on to say: “If you cross the border illegally, you should be able to be sent back. It’s a crime.”
Earlier protesters had shouted “Fire Pantaleo!” while the New York mayor, Bill de Blasio, was speaking. Their shouts continued while New Jersey senator Cory Booker was talking, forcing him to pause.
The shouts referred to Daniel Pantaleo, a New York police officer blamed for the death of Eric Garner after putting him in a chokehold five years ago. Mr Garner’s repeated cry of “I can’t breathe” became a rallying call for people protesting about police brutality, particularly that targeted against African-Americans.
Mr Pantaleo is still serving as a police officer.
The New York Post reported that between seven and ten “well dressed” members of the audience were removed from the Fox Theater.
One of them, Rev Kirsten John Foy, told the paper: “[De Blasio] has failed to provide justice for the family of Eric Garner and the city of New York.”