With his wife, Jill, and President Barack Obama at his side in the White House Rose Garden, Biden said the window for a successful campaign "has closed," noting his family's grief following the death of his son, Beau.
Still, Biden, who a spokesman said made his decision Tuesday night, positioned himself as a defender of the Obama legacy, implicitly suggesting that he still views himself as the best possible successor to the President.
In tone, the remarks sounded like the kind of speech defending staunch Democratic values that he might have given had he reached the opposite conclusion.
The vice president sent a pointed warning to the Democratic front-runner in his remarks, again apparently rebuking her for her comment in last week's CNN Democratic debate that Republicans were her enemies.
"I believe that we have to end the divisive partisan politics that is ripping this country apart, and I think we can," said Biden, who, though a crafty partisan, often worked across the aisle during nearly four decades in the Senate.
"It's mean-spirited, it's petty, and it's gone on for much too long. I don't believe, like some do, that it's naive to talk to Republicans. I don't think we should look at Republicans as our enemies. They are our opposition. They're not our enemies."
He added: "For the sake of the country, we have to work together."
'I will not be silent'
"While I will not be a candidate, I will not be silent," he said in a speech that highlighted Democratic themes on income inequality along with a call for a national movement to cure cancer. "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."
The question of whether Biden, 72, would enter the race has consumed Democrats for months, but in recent days, the vice president's long period of deliberation had begun to frustrate some in the party -- and there was rising pressure for him to declare his intentions.
The prospect of a run seemed to decline further after Clinton's commanding performance at the first Democratic presidential debate
on October 13. Her poised demeanor and deft handling of tough questions left many analysts convinced that Clinton effectively froze Biden out of the race.
Two looming political events may have affected the timing of Biden's announcement. On Thursday, Clinton appears before a Republican-led committee on Capitol Hill probing the deaths of four Americans in attacks on U.S. facilities in Benghazi, Libya, on September 11, 2012, when she was secretary of state. The vice president may not have wanted his decision to be seen as a judgment on her performance if it was made public after the hearing. Democrats are also gathering this weekend at an important party dinner in Iowa -- a must stop for presidential candidates seeking the nomination and a Biden no-show would likely have severely hampered his chances in the state.
Implicit in Biden's remarks was a realization that Clinton's position and organizational muscle in early voting states are just too strong for him to mount a credible challenge at such a late stage -- just three-and-a-half months before first votes are cast.
The vice president's running room has been further curtailed by the unexpected strength of progressive champion Bernie Sanders who is running a close race to Clinton, in the first-in-the-nation primary state of New Hampshire.
By starting a campaign so late, Biden would have faced significant obstacles in raising the millions of dollars needed to give him a chance to win, and in setting up grassroots political organizations to wage the nomination fight across the nation.
Clinton, however, had only praise for Biden, describing him in a Tweet as "a good friend and a great man. Today and always, inspired by his optimism and commitment to change the world for the better," she wrote. "She signed the Tweet "--H" signifying that she, and not a campaign aide, composed the message.
Sanders said in a statement that Biden had made a decision that he feels "is best for himself, his family and the country. I thank the vice president for a lifetime of public service and for all that he has done for our nation."
Missouri Democratic Sen. Claire McCaskill, a Clinton ally, said that Biden's move would further solidify the former secretary of state's control of the Democratic race.
"You can see from the polling numbers that have come out this week how that has certainly reassured and solidified her support among Democrats across the country," she said. "I think this will push her even further in that direction."
Democratic Senate Minority leader Harry Reid
told CNN that Biden would have been a good candidate "but he made the right decision."
And Republican front-runner Donald Trump combined a comment on Biden with a swipe at Clinton.
"I think Joe Biden made correct decision for him & his family. Personally, I would rather run against Hillary because her record is so bad," Trump wrote.
A CNN/ORC poll last week showed that Clinton held a 16 percentage point lead -- 45% to Sanders' 29% -- with Biden in the race and drawing 18% support. But with Biden removed from the list of candidates, Clinton's lead jumped to 56% to Sanders' 33%.
Though Clinton had publicly said she was giving Biden all the space and time he needed, there were signs her campaign was preparing to run against the vice president.
She has staked out several positions in recent weeks -- notably coming out against the Trans Pacific Partnership Trade deal that is backed by the Obama administration but opposed by many Democrats in a way that seemed to further narrow Biden's options.
Biden's move means that barring unexpected developments, his long political career, which includes nearly 40 years in the Senate and two terms as vice president, will end along with the Obama administration on January 20, 2017.
No genuine route to the nomination
With Biden bowing out, the Democratic nomination now comes down to a straight fight between Clinton and Sanders, assuming low-polling candidates such as former Maryland Gov. Martin O'Malley do not catch fire.
And his decision it spares Obama the awkward prospect of watching his vice president and former secretary of state battle to succeed him.
Biden's political career spans 40 years and is bookended by tragedy. Soon after he won his Delaware Senate seat in 1972, his wife and infant daughter died in a car crash. Then in May 2015, his son Beau, an Iraq war veteran and his family's hope to forge a political dynasty, died.
Though devastated by the loss, Biden's consideration of a White House campaign may have been motivated by his dying son's plea that he make a third run at the presidency.
He went through a highly public period of mourning and testing of the political waters, pouring out his heart on Stephen Colbert's late night show, and emotionally admitting at public events that he simply did not know if his family had the emotional endurance for a race.
Biden's previous two campaigns, in 1988 and 2008, barely caused a stir and foundered to a large extent because of his own indiscipline, a trait that earned him a reputation as gaffe-prone and which, allied with a garrulous temperament, led some to believe he was not of presidential caliber. Still, he was chosen for the No. 2 spot by Obama for his long experience in foreign policy and his deep knowledge of the Senate.
Biden's career will now be remembered largely for his vice presidency, in which he was in the room for all major decisions and was at Obama's side through dramas including the killing of Osama bin Laden
and the passage of health care reform. He masterminded the implementation of the $800 billion stimulus plan which Democrats credit for staving off a second Great Depression and brokered a deal in 2012 to avert the so-called fiscal cliff.
But his most lasting contribution may be the way Biden lived his life. Every time fate dealt him a blow -- including serious health issues when he had a brain aneurysm in 1988 -- he got back up, refusing to be beaten. And with a dash of Irish blarney and his love for political combat, he maintained relationships across the political aisle that now seem like a throwback to a long-gone age of civility.
His political approach is tactile, and personal, interwoven with parables of working-class life, hewn from his upbringing in the gritty Pennsylvania city of Scranton and of family life in his adoptive state of Delaware.
But after spending the better part of 40 years being talked about as a potential president, Biden will likely not be able to look back on his decision to forgo a final 2016 run, without a tinge of regret that he fell just short of the highest prize.