The hotel, with its Michelin-starred Number One restaurant, began life as a grand railway hotel in 1902.
It features in a list of only five hotels in the world including Four Seasons Hotel George V in Paris and The Lowell, New York City.
Gleneagles, located in 850 acres of Perthshire countryside, has been included in the Best Family Programme category.
Meanwhile The Flying Stag at The Fife Arms in Braemar, Aberdeenshire, which features specially commissioned portraits of Braemar residents, has been nominated for Best Bar.
The annual Best of the Best Awards recognises the top 50 hotels and figures in the hospitality industry.
Malcolm Roughead, chief executive of Visit Scotland, said: “This hat-trick of nominations reflects the strength and depth of Scotland’s position in international luxury travel and is a testament to the work of our industry in adapting to the ever-changing demands of visitors.”
Virtuoso is currently casting votes for their favourite categories. The winners of each of the ten categories will be announced at a ceremony at the Bellagio Hotel, Las Vegas on 14 August.