The surprise announcement on Sunday night signalled a potential change in approach at one of the world's largest banks.
With a market value of $159 billion, the London- and Hong Kong-listed lender is worth more than Citigroup, even though its stock has fallen under Flint's tenure.
Flint was the top choice of the board under its then-newly-appointed chairman, Mark Tucker.
The 51-year-old had been regarded as a safe choice because of his decades-long career at the bank, and he made few changes to the bank's strategy during his tenure.
But his low-key style frustrated some, according to some people within the bank, and the board decided he had to go for HSBC to keep up and get ahead of business conditions and world events.
"We've made a decision by mutual agreement. In an increasingly complex and challenging global environment, the board feels a change is needed to make the most of the opportunities before us," Tucker said in an interview.
In a statement, Flint said it had been a privilege to spend his entire career at HSBC, which he joined from college as a trainee on its international manager program.
HSBC said Flint will leave his role immediately but will be available to assist HSBC with the leadership transition.
The bank's global commercial banking head, Noel Quinn, will take temporary charge of the CEO role while a search is carried out, it added.
( With inputs from IANS )