"His lack of empathy and compassion can be summed up in a phrase I suspect he's most proud of having made famous, 'you're fired,'" Biden said in a speech that repeatedly brought delegates at the Democratic National Convention out of their seats.
"How can there be pleasure in saying 'you're fired?' He's trying to tell us he cares about the middle class? Give me a break!" Biden explained before offering his own well-used tagline: "That's a bunch of malarkey!"
"This guy doesn't have a clue about the Middle Class. Not a clue. He has no clue about what makes America Great. Actually he has no clue. Period," Biden said, inciting chants of "Not a Clue! Not a Clue!"
Biden's speech is likely to be the final major political address of his career, and he used it to also give a strong endorsement of Hillary Clinton.
"Everybody knows she is smart. Everybody knows she is tough. But I know what she is passionate about," Biden said. "I know Hillary. Hillary understands. Hillary gets it."
Entering the hall to the theme from "Rocky" and a prolonged standing ovation, he hailed President Barack Obama as "the embodiment of honor, resolve and character, one of the finest presidents we have ever had."
Flatly rejecting Trump's views both on foreign policy and the economy, Biden scorched the GOP candidate as the most unprepared nominee ever, and suggested he could put nothing less than the international order at risk.
"The times are too uncertain to elect Donald Trump as President of the United States," Biden said. "No major party nominee in the history of this nation has ever known less or has been less prepared to deal with our national security."
The remarks came hours after Trump raised alarms in foreign policy circles for his overtures to Russian President Vladimir Putin.
"We cannot elect a man who belittles our closest allies while embracing dictators like Vladimir Putin," Biden insisted. "A man who confuses bluster with strength, we simply cannot let that happen as Americans. Period."
Like Obama, Biden is predicted to have a regular campaign presence leading up to November's vote.
"I'm going to be living in Pennsylvania and Ohio and Michigan" leading up to the election, he said on MSNBC Wednesday -- all states where his blue collar appeal would resonate. That tour is set to begin August 15, when Biden campaigns alongside Clinton in his hometown of Scranton, Pennsylvania.
Biden acknowledged his final convention address as an elected official was a bittersweet moment, coming only a year after the loss of his eldest son, Beau.
Noting his son had placed his name into nomination during the 2008 and 2012 conventions, Biden said he had gathered strength from his family and supporters, including the President and first lady.
"I've been made strong at the broken places," he said, quoting Ernest Hemingway.
Biden said he'd joked with Obama they were all speaking in the shadow of First Lady Michelle Obama's remarks on Monday.
"I don't know where you are, kid, but you are incredible," Biden told Mrs. Obama, who was watching Wednesday's convention proceedings from her mother's house in Chicago.