Mr Lewis, who was been Bank of America's CEO since April 2001, is to retire from the company on December 31st 2009.
The final year of the sixty-two year old's tenure saw him attacked for several of his acquisitions, which infamously included paying $29 a share to buy brokerage giant Merrill Lynch on the same day, September 15th 2008, that Lehman Brothers announced it was bankrupt.
Since that date Bank of America shares have fallen by 50 per cent as a variety of government agencies began investigations into possible wrongdoings in the Merrill Lynch deal.
New York attorney general Andrew Cuomo, whose office is one of the agencies probing the agreement, said Mr Lewis's resignation would not affect his decision into whether he will bring charges against Bank of America executives.
In his resignation statement Mr Lewis defended his record and said positive results were beginning to emerge for the bank.
"The Merrill Lynch and [US home lender] Countrywide integrations are on track and returning value already," he said.
Merrill Lynch contributed almost one-quarter of Bank of America's first-half profit for 2009 and Mr Lewis told employees that the deal was being vindicated.
"I am gratified that even some of the critics of our acquisition of Merrill Lynch have come to acknowledge how well the deal is working out for our clients," he said.
Under his leadership Bank of America tripled in size to become the biggest US lender and spent more than $130 billion on a variety of acquisition deals.
But his departure sees him become another high-profile casualty of the financial crunch.
Other CEOs who have had to leave their posts under pressure include Stanley O'Neal of Merrill, Charles Prince of Citigroup and James Cayne of Bear Stearns.
Bank of America said it aims to name a successor to Mr Lewis before his departure date.
By Claire Archer