Thursday's announcement marks the unofficial end of the chaotic early phase of the 2020 presidential season. The field now features at least 20 Democrats jockeying for the chance to take on President Donald Trump next year. Several lesser-known candidates may still join the race.
Biden, a 76-year-old lifelong politician, becomes an instant front-runner alongside Jewish Vermont Sen. Bernie Sanders, who is leading many polls and has proved to be a successful fundraiser. Among Democrats, Biden has unmatched international and legislative experience, and he is among the best-known faces in US politics.
But the anti-establishment wave that swept Trump into office has not been kind to either party's statesmen. Biden's team worries about his fundraising ability and his tendency to commit gaffes. His centrist approach in a party moving left on major policy debates raises questions about his appeal.
Four years Trump's senior, Biden would be the oldest person ever elected president should he win. Yet his allies believe the skeptics will ultimately warm to his strong connections to the Obama years.
Biden has said he would campaign as an "Obama-Biden Democrat," who is as pragmatic as he is progressive. He's aiming to be a conduit between working-class white voters and the younger, more diverse voters who backed Obama in historic numbers.
The Republican Party wasted no time seeking to undercut Biden's record, releasing a video on Wednesday questioning economic growth under Obama and Biden while resurrecting conservative arguments against Obama's health care law and a failed investment in green energy company Solyndra.
The video ends with the words, "Joe Biden: Backwards, not forwards."
Yet privately, Trump allies have warned that Biden might be the biggest re-election threat given the former vice president's potential appeal among the white working class in the Midwest, the region that gave Trump a path to the presidency.
The Republican video notably does not argue a Biden candidacy would lead to socialism, as Trump and his backers have said would happen with many in the large 2020 Democratic presidential field.
Biden is paying special attention to Pennsylvania, a state that swung to Trump in 2016 after voting for Democratic presidential candidates for decades.
The former vice president will be in the state three times within the opening weeks of his campaign. He'll be in Philadelphia on Thursday evening headlining a fundraiser at the home of David L. Cohen, executive senior vice president of Comcast. Biden is aiming to raise $500,000 at the event.
He will hold an event in Pittsburgh on Monday and will return to Philadelphia in the next two weeks for a major rally.
His plans were described by people who spoke on the condition of anonymity because they weren't authorized to discuss his schedule and fundraising goals.
With a record that stretches half a century, Biden's challenges are easy to find.
Most recently, he struggled to respond to claims that he touched 2014 Nevada lieutenant governor nominee Lucy Flores' shoulders and kissed the back of her head before a fall campaign event. A handful of other women have made similar claims, though none has alleged sexual misconduct.
Biden initially said he didn't recall the Flores incident but credited her with coming forward. He took a different approach in a subsequent statement, saying, "Never did I believe I acted inappropriately."
Biden later pledged in an online video to be "much more mindful" of respecting personal space but joked two days later that he "had permission" to hug a male union leader before addressing the group's national conference.
The episode offered a stark reminder of Biden's proclivity to gaffes and his long record in public office that has never felt the full glare of the spotlight that comes along with being a presidential front-runner.
His first White House bid in 1988 ended after a plagiarism scandal. He dropped out of the 2008 race after earning less than 1 percent of the vote in the Iowa caucuses. Later that year, Obama named Biden as his running mate.
More recently, Biden's willingness to work with Republicans has caused him political headaches.
He was forced to walk back a comment last month that Vice President Mike Pence is "a decent guy" after intense blowback from liberal activists upset with Pence's opposition to gay rights.
In recent weeks, Biden also has been repeatedly forced to explain his 1991 decision, as Senate Judiciary Committee chairman, to allow Anita Hill to face difficult questions from an all-male panel about allegations of sexual harassment against Supreme Court nominee Clarence Thomas, who later was confirmed to the high court.
Biden has since apologized for his role in the hearing. But in the #MeToo era, particularly after the contentious confirmation of Supreme Court Justice Brett Kavanaugh, the episode remains a significant political liability.
Likewise, Biden once played a key role in anti-crime legislation that had a disproportionately negative impact on African Americans. And while several 2020 Democratic contenders have embraced the possibility of reparations to African Americans for slavery in recent weeks, Biden last month struggled to explain comments he made as a freshman senator in 1975 about the school busing debate.
Biden's 2020 bid comes four years after he opted against challenging Hillary Clinton in the 2016 Democratic contest.
In a book he wrote about conversations with his dying son, he opened up about the difficult choice to sit out the last presidential race: abandon a careerlong quest for the presidency or lose precious time with a family he'd held together through tragedy, from his first wife's and his daughter's deaths in a 1972 car accident to son Beau Biden's 2015 death from cancer.
"He was worried that what I'd worked on my whole life, the things that mattered to me the most since I was a kid, that I'd walk away," Biden said of his son.
Ultimately, the draw to take on Trump in 2020 was too strong.