The global banking giant says it needed to make changes to address a “challenging global environment”.
Mr Flint has bowed out after a year-and-a-half at the helm “by mutual agreement”.
He will immediately cease his day-to-day responsibilities at HSBC, but will help with the transition as Noel Quinn takes over as interim chief executive.
Chairman Mark Tucker thanked Mr Flint for his “commitment” and “dedication”.
He added: “In the increasingly complex and challenging global environment in which the bank operates, the board believes a change is needed to meet the challenges that we face and to capture the very significant opportunities before us.”