“We are in the battle for the soul of this nation,” he said in his campaign video, released on Thursday morning.
“If we give Donald Trump eight years in the White House, he will forever and fundamentally alter the character of this nation – who we are – and I cannot stand by and watch that happen.”
Best-known for serving as vice president during Barack Obama’s presidency, Mr Biden became an immediate frontrunner for the Democratic candidacy.
Amid the Trump presidency, a flurry of fresh faces and an increasingly progressive Democratic Party, Mr Biden’s campaign will try to convince voters that the US needs an experienced, calm figure that can make the US take a deep breath and pull its act together again, according to analysts of US politics.
And Mr Biden has experience – he’s been on the political scene for decades. Born in 1942, he was first elected to the US Senate in 1972 for the state of Delaware – becoming the sixth-youngest senator in American history.
He was re-elected six times and only resigned to become vice president in 2009.
This is Mr Biden’s third attempt to run for the presidency, after his 1988 and 2008 presidential campaigns.
His life has been notoriously scarred by tragedies. In December 1972, just a few weeks after his first election, his wife and one-year-old daughter died in a car accident in Delaware. In 2015, one of his two sons who survived the accident died at 46 after a two-year battle with brain cancer – and as a consequence, Mr Biden decided not to run for president in 2016.
He is widely perceived as relatable, empathetic and authentic. Mr Biden has occasionally emphasised his blue-collar roots and the fact that he consistently ranked as one of the least wealthy members of the Senate – although he has recently earned millions of dollars through a lucrative book deal and selected paid speaking.
In a 2009 interview, Mr Obama compared Mr Biden’s efforts to a basketball player “who does a bunch of things that don’t show up in the stat sheet”.
He is popular in some places Democrats have lost, such as working-class swing states Wisconsin, Michigan and Pennsylvania, as well as with minorities and older voters, according to a recent poll.
But his campaign faces many challenges. Politically, Mr Biden is a centrist in an increasingly progressive Democratic Party. “I'm an Obama-Biden Democrat, man,” Mr Biden told reporters earlier in April. “And I'm proud of it.”
He is likely to face scrutiny for being in favour of capital punishment and for supporting a 1994 crime bill that experts say contributed to an era of mass incarceration. He voted in favour of the Iraq War in 2002 but opposed the surge of US troops in 2007.
During his time as vice president, he supported deficit spending for fiscal stimulus in 2009, increased infrastructure spending, and reduced military spending in 2014.
Recently, some women have claimed that he touched them in an overly familiar manner without their consent. Mr Biden has struggled to respond, saying that inappropriate behaviour “was never my intention”, and pledging to be “much more mindful” of respecting personal space.
His age and experience are also potential challenges. If elected, Mr Biden would become the oldest president in US history.
And as an increasingly progressive Democratic Party craves new faces, it’s unclear whether its base will support an older white man who has spent half a century in Washington.