Mr Klain has served as a top aide to Mr Biden since the 1980s in the Senate and later when he was vice-president.
The ultimate Washington insider, Ron Klain was also a senior White House aide to Barack Obama and chief of staff to Vice-President Al Gore.
He was played by actor Kevin Spacey in the movie Recount, about the presidential election of 2000.
The White House chief of staff – who manages the president’s daily schedule and is often described as his gatekeeper – is a political appointee that does not require confirmation by the Senate.
Biden paid tribute to Ron Klain in a statement issued by his transition team on Wednesday.
“His deep, varied experience and capacity to work with people all across the political spectrum,” said Mr Biden, “is precisely what I need in a White House chief of staff as we confront this moment of crisis and bring our country together again.”
In the same statement, Mr Klain said he was “humbled” by the president-elect’s confidence in him.
“I look forward to helping him and the vice president-elect assemble a talented and diverse team to work in the White House, as we tackle their ambitious agenda for change, and seek to heal the divides in our country,” said Mr Klain.
Who is Ron Klain?
Mr Klain served as chief counsel on the Senate Judiciary Committee from 1989-92 when Mr Biden was chairman.
He was also an adviser and speechwriter on Mr Biden’s unsuccessful 1988 and 2008 White House campaigns.
Mr Klain served as chief of staff to Mr Biden from 2009-11 during his tenure as vice-president in the Obama White House.
He later served as “Ebola czar” under Mr Obama during a minor outbreak of the deadly disease in 2014.
The longstanding Democratic operative was also involved in both of Bill Clinton’s presidential campaigns and was an adviser to John Kerry’s failed White House run in 2004.
He has been a presidential debate coach for Mr Clinton, Mr Gore, Mr Kerry, Mr Obama, Hillary Clinton and Mr Biden.
His role as chief of staff to Mr Gore, who retracted his initial concession in the disputed White House election of 2000, was turned into the HBO drama Recount.
“The plural of chad is chad?” Mr Klain, played by Spacey, asks at one point in the film, referring to the fragments of punched ballots that became critical to the tally in Florida.
Mr Gore’s Republican opponent, George W Bush, was ultimately declared the winner.
Ron Klain often tweets about the episode, only last year posting: “People frequently tell me that I should ‘get over’ the 2000 election and the recount. I haven’t, and I don’t think I ever will.”
After his work on the Gore campaign, Mr Klain worked as a high-powered Washington lobbyist for a mortgage giant and a drugmaker that was under congressional investigation.
Does Klain have any political baggage?
He fell out with the now-president-elect five years ago after throwing in his lot with Mrs Clinton’s campaign back when Mr Biden, then-US vice-president, still hoped to compete for the party nomination.
“It’s been a little hard for me to play such a role in the Biden demise,” Mr Klain wrote of the man he had served as chief of staff in an email to Clinton presidential campaign chairman John Podesta in October 2015.
“I am definitely dead to them – but I’m glad to be on Team HRC,” he added, using Mrs Clinton’s initials.
The message was disclosed by Wikileaks following a hack and Mr Klain refused to comment on the controversy in August when it was reported by news outlet, Politico.
Mr Klain has since worked his way back into Mr Biden’s good graces.