The event in Scranton, a town in Northeast Pennsylvania that both Clinton and Biden have ties to, marked the first time the vice president has hit the campaign trail with Clinton.
Biden, in his standard long-winded and free-wheeling style, blasted Trump for "outrageous" and "dangerous" comments he made about President Barack Obama being the "founder" of ISIS.
"If my son were still in Iraq and I say to all those who were there, the threat to their life has gone up a couple of clicks, it has gone up a couple clicks," Biden said, referencing his late son Beau, who died of cancer in 2015.
At one point, Biden noted there is an aide who follows him at all times with the nuclear launch codes should it be necessary for him to use them if Obama were not able to.
"He is not qualified to know the code!" Biden said of Trump, calling him "totally unqualified" to be president. "He can't be trusted!"
Biden argued that comments like that, as well as glowing statements Trump made about dictators and strongmen like Vladimir Putin -- "He would have loved Stalin," Biden said -- show that the Republican nominee is unfit to be president.
"No major party nominee in the history the United States of America ... has known less or been less prepared to deal with our national security than Donald Trump," Biden said. "And what actually amazes me that he doesn't seem to want to learn it. I really mean it. He doesn't seem to want to learn it."
Clinton, who introduced Biden, touted the vice president as a hometown hero who has always remained true to his roots while slamming Trump for not understanding those same origins.
On the economy, Clinton said even before Trump laid out his economic agenda last week, she "didn't think it was going to be good for working Americans."
"But it turned out to be worse than I even imagined," she said, adding, "I know, friends should not let friends vote for Trump."
Clinton argued that Trump "has been all over the place on ISIS" and noted that he was giving a speech about the terror group on Monday.
"We will wait and see what he says today. Sometimes he says he won't tell anyone what he will do because he wants his plan to be quote, secret, then it turns out the secret is he has no plan," Clinton said to laughs.
Biden, 73, has emerged as one of Clinton's most powerful surrogates. The former Delaware senator's ability to connect with middle- and working-class voters will be especially potent in battleground Rust Belt states like Pennsylvania and Ohio, where economic frustrations are running high.
Trump has made this region a focal point of his general election strategy and is banking on the populist economic message that helped propel him to the top during the primaries to win him independents and Reagan Democrats on Election Day.
The event Monday was both a political rally and a homecoming for Biden and Clinton.
Biden grew up in Scranton and spent summers in the town after moving to Delaware at age 10. Clinton, while growing up outside of Chicago, spent summers at Lake Winola outside of the Pennsylvania town.
"The story of the Rodham's and the Biden's isn't unique. What is unique is the country where those stories were written," Clinton said Monday. "No matter what Donald Trump says, America is great. And the American dream is big enough for everyone to share in its promise."
Clinton said "Joe grew up over on North Washington Avenue and no matter how far he travels, he never forgot where he is from," casting him as "a fighter for everyone who needs a champion, for towns like Scranton and above all a fighter for families."
Clinton also said that she would ask Biden to help her administration, should she be elected in November.
Biden, after his son's death, launched the Cancer Moonshot Initiative last year, aiming to double the research breakthroughs in curing cancer.
"His wonderful son Beau, a great father, a great public servant, a great human being, passed away last year, so this is personal to Joe Biden," Clinton said. "That is why he is fighting so hard to made a difference. And If I am elected this fall, I am going to ask Joe to continue the important work he has begun."
Monday's event was originally scheduled for last month, but was canceled in the aftermath of an ambush in Dallas that killed five police officers.
Delaware Democratic Sen. Chris Coons told CNN in a recent interview that there is no one better than Biden at connecting with voters who feel "left out and overlooked."
"If I were campaigning in Pennsylvania for the United States Senate, there is no one I would want next to me more than Joe Biden," Coons said. "No one works a diner, no one works a volunteer fire hall, no one works a senior center better than Joe Biden."
Famous for his gregarious personality and unfiltered style, Biden is the latest in a string of high-profile Democrats to hit the road for Clinton. Obama held his first joint event with his 2008 rival in North Carolina last month, and Clinton has also picked up endorsements from popular liberals like Massachusetts Sen. Elizabeth Warren and primary rival Bernie Sanders, the Vermont senator.
For many of Biden's fans and long-time allies, the vice president's appearance at the convention was bittersweet. Biden ran for president in 1988 and 2008, and last year, he contemplated launching a third White House bid.
But the death of his son made it impossible for Biden to pursue that dream. With his wife, Jill, and Obama by his side, Biden announced at the White House Rose Garden in October
that he had finally closed the door on this decades-old political aspiration.
"While I will not be a candidate, I will not be silent," Biden said. "I intend to speak out clearly and forcefully, to influence as much as I can where we stand as a party and where we need to go as a nation."
Lisa Goodman, president of Equality Delaware, watched Biden speak inside the convention arena last month. She described the moment as an emotional one for the Delaware delegation, particularly as they listened to Biden speak about his son.
"It was bittersweet for us as Delawareans -- it might be the last time that we ever see him on a stage like this," Goodman said. "I think that Joe is nothing if not heart. And his heart was broken. And as he says, he'll be stronger in the broken places but it's going to take time."
Steve Schale, a longtime Democratic strategist who was a part of the Draft Biden 2016 effort, said when he recently saw Biden, there was no question that the vice president was "at complete peace with the decision he made in October" -- and now wholly dedicated to the mission of electing Clinton to the White House.
Trump is going hard after Pennsylvania's 20 electoral votes
, campaigning last week in the western part of the state, hoping his anti-trade and anti-establishment message sells well with blue-collar workers in the Rust Belt.
"We're going to watch Pennsylvania," he said in Altoona on Friday. "Go down to certain areas and watch and study and make sure other people don't come in and vote five times. If you do that, we're not going to lose. The only way we can lose, in my opinion -- I really mean this, Pennsylvania -- is if cheating goes on."