Barclays and four individuals, including former boss John Varley, have been charged with conspiracy to commit fraud relating to the bank's emergency fundraising during the financial crisis.
The Serious Fraud Office (SFO) said it had brought the charges against the bank itself as well as ex-chief executive Mr Varley, 61, Roger Jenkins, also 61, who is the former executive chairman of Investment Banking and Investment Management in the Middle East and North Africa for Barclays Capital, as well as two former senior executives, Thomas Kalaris, 61, and Richard Boath, 58.
The SFO has also charged Barclays plc, Mr Varley and Mr Jenkins with the provision of unlawful financial assistance.
It said the charges relate to the bank's fundraising in 2008, which saw Barclays raise emergency capital from Qatari investors as the financial crisis sent the sector into meltdown.
The SFO charges come after a five-year investigation and centre on the bank's move to raise cash from Qatari investors Qatar Holding and Challenger Universal in June and October 2008, and a 3 billion US dollar (£2.4 billion) loan made available to the State of Qatar in November of that year.
Barclays said it is "considering its position in relation to these developments".
The bank added: "Barclays awaits further details of the charges from the SFO.
"The SFO has informed Barclays that it has not made a decision as to whether it will also bring charges against Barclays Bank Plc in respect of the loan."
The Financial Conduct Authority (FCA) has also reopened its probe into the Qatari fundraising deal and is understood to be reviewing new evidence which could prompt it to reconsider a £50 million fine against the banking giant four years ago.
The emergency funds raised by Barclays allowed it to avoid a government bailout in 2008 at a time when rivals Lloyds Banking Group and Royal Bank of Scotland were forced to rely on a taxpayer rescue.
Mr Varley, who was chief executive between 2004 and 2011, headed the bank at the time of the fundraising, while Mr Jenkins is also said to have played a key role in orchestrating the deal.
Mr Kalaris - an American banker living in London - used to lead the bank's wealth and investment management division, while Mr Boath was the former European head of financial institutions group at Barclays.
The defendants will appear at Westminster Magistrates' Court on July 3.
The way the bank secured the investments in 2008 has since been mired in controversy.
Investigations have focused on two "advisory services agreements" worth £322 million, which Barclays agreed to pay the Qatar Investment Authority.
The FCA slapped a £50 million penalty on the bank in 2013 after finding that Barclays had failed to disclose arrangements and fees it paid to the Qatari investors.
Barclays contested the fine and the challenge was put on hold while the SFO conducted its investigation, but that stay has been lifted.
The United States Department of Justice and the US Securities and Exchange Commission have also been carrying out investigations over the payments.
Barclays is meanwhile facing legal action from financier Amanda Stavely to recoup £700 million in advisory fees from Barclays she claims her firm, PCP Partners, is owed relating to the 2008 fundraising, which Barclays is defending.
The charges will come as a further headache for current Barclays boss Jes Staley after a series of recent blows, with the chief executive also facing a regulatory investigation into his own conduct after he attempted to identify a whistleblower.
Lord Myners, who was city minister between 2008 and 2010, told BBC Radio 4's Today programme Barclays bosses were "vehement" at the time that they did not want a government bailout.
He said: "I think firstly there was a real fear on their part that this was nationalisation, it was political, they didn't want anything to do with a Labour government.
"Secondly, they realised that the terms we were imposing meant that pay for their senior bankers and bonuses and options were going to be substantially reduced.
"So they managed to find capital from elsewhere.
"That surprised a lot of people, and that is the background to the investigation that the SFO has now been conducting for the last five years."