In a statement, Bob Diamond says, "The external pressure placed on Barclays has reached a level that risks damaging the franchise - I cannot let that happen."
Barclay, Britain's third-largest bank, was recently fined almost half a billion dollars for participating in a global manipulation of benchmark interest rates.
Diamond's resignation was effective immediately. Outgoing chairman Marcus Agius will lead the search for a new CEO, despite having announced his own imminent departure a day earlier, declaring that "the buck stops with me".
Anthony Jenkins, currently chief executive of Barclays retail and business banking, is the most likely internal candidate to replace Diamond, said Oriel Securities analyst Mike Trippitt. However, the firm may choose to look outside for a new leader to turn the page on the scandal.