Listing global irritants like mass migration, terrorism, climate change, Biden said those factors are leading to leaders "peddling xenophobia, nationalism, and isolationism," including in the United States.
"To play to our fears rather than, as Abraham Lincoln said, to appeal to our better angels, build walls instead of bridges -- it has been un-American what we have been seeing," Biden said in Dublin. "It's not who we have become. It is not who we are."
Biden's remarks came as the world reacts to the United Kingdom's vote to exit the European Union. He warned against global trends toward nationalism "in Europe and other parts of the world."
Earlier Friday, Biden said the U.S. "respects" the UK's decision, but admitted he and President Barack Obama had wished for a different outcome.
"I want to ensure all of you in this room that America's special bond with the United Kingdom runs deep and will endure. And our relationship with Ireland and the European Union will remain the cornerstone of our global engagement," Biden said at Trinity College in Dublin.
Biden is on a mutli-day trip to Ireland, meeting with leaders there and visiting sites in the West that relate to his ancestry. Before the Brexit vote, he discussed the potential ramifications of the referendum with the Irish Prime Minister and President.
The White House was vocal in its opposition to Britain's exiting the EU, a rare foray into another country's political affairs. Obama took the unusual step of traveling to London in April to make his case against leaving, drawing on the personal ties between the two countries.
Biden on Friday issued similar warnings against those fears in the United States, making plain allusions to Donald Trump.
"Some politicians find it convenient to scapegoat immigrants rather than welcoming them," he said.
Drawing on the powerful history of Irish immigration to the U.S. — including by his own relatives — Biden expounded upon the importance of allowing those fleeing hardships entry into the country.
"We're defined by a common creed that says to our children that if they work hard, if they struggle, if they are loyal, if they are courageous — they will have an opportunity to live a better life than the generation before them," Biden said. "It's defined by a simple belief that anything is possible. And it's a belief shared by the vast majority of immigrant families that have come to the United States from many other nations over the years."