Some 1.8 million people are expected to use the John Muir Way in the first year after it is opened this spring by First Minister Alex Salmond.
The trail is named after the Scottish-born environmentalist who emigrated to the United States and made his name as the founding father of American national parks, and runs from his birthplace in Dunbar, East Lothian, to Helensburgh, Argyll and Bute.
Currently, the Fife Coastal Path, parts of which are visited by around 500,000 a year, is Scotland's most popular trail, followed by the West Highland Way which attracts a total of around 90,000 users.
Experts believe more people will visit the John Muir Way due to its proximity to the densely-populated Central Belt.
Many parts of the path have been established for some time and the new 130-mile route - which opens on April 21 to mark the centenary of Muir's death in 1914 and his birthday on April 21, 1838 - connects them.
Glamis Consultancy was commissioned by Scottish Natural Heritage, which is responsible for the project, and it estimated that in its first year around 1.8 million people would walk along some sections and 9000 do the walk from end to end.
Around 34,000 people complete the world famous 96-mile West Highland Way every year, and about 5000 the 117-mile Fife Coastal Path.
Ron McCraw, project manager for the John Muir Way at SNH, said the walk passed a rich variety of scenery across the central belt and was accessible to several million people. "It goes along canal corridors, water bodies, passes over hills and around hills. Along the way there are fantastic views of farmland, cityscapes, the Forth, the Clyde. Together it gives a lovely picture of the central belt of Scotland," he said.
"We want to awaken in people the philosophy that John Muir had about nature. He was inspired by the magnificence of the Rocky Mountains in the United States, but he was also inspired by what was in his back yard. We think it will be a very special route."
Mr McCraw said much of the terrain was not difficult, though there were some harder parts, including Gouk Hill, between Balloch and Helensburgh, but he also described Gouk Hill as one of the walk's highl ights with spectacular views from its summit over the Clyde and the southern end of Loch Lomond.
Other notable sections, he said, included Croy Hill, part of the Antonine Way near Cumbernauld, where walkers can see the site of a Roman fort; a stretch between Bo'ness and Blackness Castle on the shore of the Firth of Forth; and a section going under the Forth Bridge at South Queensferry, near Edinburgh.
Cyclists can also ride along the trail, though alternative paths are provided in some parts to avoid damaging historical sites.
Keith Geddes, chairman of the Central Scotland Green Network (CSGN) partnership, an initiative set up by the Scottish Government to develop environmental schemes in central Scotland and which spearheaded the concept of the route, said he hoped the trail would raise awareness about John Muir's achievements.
"John Muir is considered one of the patron saints of twentieth-century American environmental activity," he said. "He is noted for being a conservationist, naturalist, geologist, inventor and explorer. However, despite the magnificent efforts of East Lothian Council, the John Muir Trust and the John Muir Museum in Dunbar, Americans still tend to know more about him than Scots.
"This is why the new route is a fitting way to celebrate a man who through his life, writings and legacy, could inspire a new generation of Scots to recognise the value of nature and the outdoors."