Kirby, who joined HS2 from Network Rail two and half years ago, was the highest paid civil servant in the UK reportedly earning £750,000 a year.
While working as chief executive at Europe’s largest infrastructure project he enlisted many colleagues from Network Rail where he had worked for 11 years.
Kirby leaves just weeks before the transport secretary is expected to make a key decision on phase two of the route, from the West Midlands to Leeds and Manchester, this autumn.
David Higgins, chairman of HS2, said the search for a successor would be conducted at the same time as it searches for a chief operating officer, a newly created position.
“Simon Kirby used his vast experience to recruit and shape a world-class team which over the coming years and decades will turn HS2 into a reality that will be of lasting benefit to this country,” said Higgins.
Kirby said: “I am hugely proud to be joining one of the world’s great engineering companies at an exciting time in its development.
“The ability to deliver major programmes on time and to budget is essential, and I am looking forward to bringing my experience to bear on these complex challenges and to leading the current programme of industrial transformation.”