Bank of America plans to cut between 30,000 and 35,000 jobs over three years following the completion of its takeover of Merrill Lynch.
The reduction could affect about 11% of their combined workforce of 308,000.
Bank of America said the move would reflect both post-merger efficiency savings, and "the weak economic environment" which had hit business.
The $US50 billion takeover of Merrill was announced in September. It came after Merrill had seen $US40 billion losses due to bad debt connected to the downturn in the US housing market.
Bank of America said the job cuts would come across both businesses, although it said it could not give exact numbers until early 2009.
The takeover has already gained shareholder approval and is due to be completed in the New Year.
The combined company will be America's largest bank by assets.
The announcement in September of its takeover by Bank of America came on the same weekend that a rival investment bank, Lehman Brothers, said it was going into bankruptcy protection.
Thursday's job loss announcement comes three weeks after Citigroup said its job cuts would now total 75,000.