The Wall Street firm said Ina Drew, who oversaw the London-based division responsible for the trading mistake, will leave after more than 30 years.
Matt Zames, the bank's co-chief of global fixed income in its investment bank, will take over from Ms Drew.
On Sunday, JPMorgan boss Jamie Dimon said he was "dead wrong" to dismiss concerns about trading at the bank.
It had been reported on Monday that Ms Drew, one of JPMorgan's best-paid executives, had offered her resignation several times following disclosure of the losses last Thursday.
However, in a statement issued in New York, Mr Dimon said: "Ina Drew has been a great partner over her many years with our firm. Despite our recent losses in the CIO, Ina's vast contributions to our company should not be overshadowed by these events."