The Democratic presidential candidate made the remarks on Trump's supporters at a campaign rally in St Paul just days before the November 3 election.
The noisy MAGA fans crashed Biden's rally by honking their horns as he discussed mask-wearing, causing him to lose his calm and shoot an outraged response.
"Dr Fauci called for a mask mandate last week. This isn't a political statement like those ugly folks over there, beeping the horn," Biden said.
"This is a patriotic duty for God's sake! Look, in his own words, as I said, the president knew back in January how extremely dangerous and communicable this disease was."
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An angry Biden went on to discuss the noise two more times during his speech.
Biden's comment happened less than a minute after he said: "We need a president who will bring us together, not pull us apart."
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Details for the invite-only drive-in rally were sent out to a shortlist of party activists.
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Cars at the gathering were socially distanced and parked about 10 to 20feet apart.
Outside the border fence, a crowd of Trump supporters assembled to wave flags and display signs in support of the Republican president.
Biden also rebuked Trump fans as "chumps" when they tried to crash his drive-by rally in Pennsylvania last weekend.
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Critics of the former vice president attacked him for imitating Hillary Clinton's notorious "basket of deplorables" comment during her 2016 presidential campaign.
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"I guess calling those who support a different political candidate ’chumps and ugly folks’ is a step up from ‘deplorables’," tweeted veteran T Lee Humphrey.
Podcaster Derek Hunter mocked Biden's comments in a tweet written in the candidate's "voice": "I will end the name-calling and bring the country together, unlike those ugly folks over there, those chumps who disagree with me.
"They probably work in the oil and gas industry and are whining that I'm going to put them out of work. Oh well, screw them," he tweeted. Jason Lewis, a Republican running for the US Senate in Minnesota, showed skepticism about Biden's capacity to unite the country after he insulted his opponent's supporters.
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Trump claimed on Friday that only he could “protect America” from Joe Biden “surrendering to the radical left” in a closing pitch to voters.
In an op-ed published, the president pleaded to voters with his record in the White House over the past four years.
“This country has seen politicians like Biden before. He will surrender U.S. jobs to foreign countries, surrender our future to the virus, and surrender our country to the radical, socialist left,” he claimed.
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