The Hollywood actor, his wife Grace Hightower and America's First Lady, Michelle Obama, hosted a dinner to raise donations for President Obama's re-election campaign at New York's Greenwich Hotel.
De Niro took to the stage in front of guests including movie mogul Harvey Weinstein and hip-hop supercouple Beyonce and Jay-Z, but his speech fell flat when he made a joke he made about the wives of Republican presidential candidates Newt Gingrich, Rick Santorum and Mitt Romney.
Before introducing the First Lady to the stage, he said, "Callista Gingrich. Karen Santorum. Ann Romney. Now do you really think our country is ready for a white first lady?"
Michelle Obama's aides weren't happy with the quip, telling CNN, "We believe the joke was inappropriate," and De Niro has now apologised for his comment in a statement.
He says, "My remarks, although spoken with satirical jest, were not meant to offend or embarrass anyone, especially the first lady."