Hector Sants is to stand down as chief executive of the Financial Services Authority.
He will leave the regulator at the end of June, the FSA confirmed.
The FSA has been criticised for its failure to regulate the UK's financial services sector effectively before the 2008 banking crisis.
Chancellor George Osborne has plans to abolish the agency, with the Bank of England taking over much of its responsibilities.
Sants was appointed chief executive in July 2007. He left Credit Suisse to join the FSA in 2004.
In January Sants said that he had not intended to become the head of the financial regulator, saying he was "talked into" applying for the job.
The FSA said that Sants "led the radical overhaul of the FSA’s pre-crisis approach to regulation, to a more proactive, intensive and judgment-led approach".
Sants had previously announced his resignation in 2010, but agreed to stay on as CEO after the government announced its plans to separate the FSA's functions into two new bodies, the Financial Conduct Authority (FCA) and the Prudential Regulation Authority (PRA).
Announcing his resignation for the second time on Friday, Sants, said:
"When I agreed to stay on as CEO in 2010, I committed to stay and deliver an orderly transition to the government’s new regulatory structure. The project is now firmly on track and with the establishment of twin peaks within the FSA I will have achieved that goal.
"Now is the right time to hand over to those who will deliver the long term goals of the future PRA and FCA.
"I am proud of what the FSA has achieved during my time in charge, through what have been incredibly challenging times. I would like to thank all of my colleagues for their dedication, support and hard work. I know I leave the organisation in very capable hands."
Adair Turner, FSA chairman, said:"The major reforms made within the FSA since the financial crisis and the progress in delivering the government’s plan would not have been possible without Hector.
"He is a truly outstanding public servant of great integrity and has provided the FSA with dedicated leadership and focus through extremely turbulent times."
Andrew Tyrie, the chairman of the Treasury select committee, said: “Hector was at the helm during a uniquely difficult period for the FSA. In that time he made a major contribution, showing complete commitment and dedication to public service.
“The directness of his explanation of decisions, not least in front of the Treasury Committee, bolstered accountability and the FSA’s authority.”