Dr Gordon Rintoul has overseen an £80 million overhaul of the Chambers Street site, which was completed earlier this year.
The radical changes to modernise exhibition spaces, create new galleries and open up previously sealed-off parts of the building have seen it become the busiest attraction in Scotland.
More than 2.2 million visitors are now being recorded annually at the museum, which has also become the busiest museum in the UK outside London.
Dr Rintoul, who was awarded a CBE in 2012, said: "The transformation of the museum has been far more than successful than any of us who first planned it could have dreamt.
"I don't think anyone could have it envisaged our visitor numbers increasing more than three fold from the 700,000 we used to get.
"The really interesting thing is that with most projects in the museum world you get a real boost in visitor numbers when you open a redevelopment and then it fades away to extent.
"We've managed to do something pretty unparalleled as our numbers have gone up and stayed up.
"The visitor experience at the National Museum now is dramatically different to before we started work on the project. I've no doubt it will be very different again in another 10 or 20 years.
"No museum of this size, scale and operation can ever stand still. You need to continually think about re-inventing yourself. The key thing is keeping a focus on the visitors as that's really what we're all about.
"The developments that have taken place here and elsewhere in Edinburgh over the last 15 years, means the city now has the strongest year-round tourism offer in the whole of the UK."
Dr Rintoul, who will leave next March after 18 years in the role, has also led the transformation of the National Museum of Flight, in East Lothian, including the acquisition of a former British Airways Concorde in 2004.
Other recent acquisitions include the Galloway Hoard of Viking-age treasures, which were secured for the nation following a £2 million appeal after being discovered on church land in Dumfriesshire.
Dr Rintoul, who was born in Glasgow and studied at Edinburgh University, said it felt like the right time for a "natural break" after the completion of the masterplan project earlier this year, but insisted he had no plans to retire.
He added: "I have spent my career in museums and the cultural sector, and allied areas like tourism. I'm keeping my thoughts open."
Bruce Minto, chair of the museum's board of trustees, said: "Gordon's leadership has helped to create a strong, dynamic and ambitious organisation which delivers significant cultural, educational and economic impact throughout Scotland and beyond.
"The transformation of the National Museum of Scotland is, undoubtedly, his flagship achievement; an enormous undertaking which could not have been realised without his vision, talent and determination."