The Perthshire restaurant also came ninth in the UK-wide list compiled by The Good Food Guide, said to be highly regarded by both chefs and restaurant-goers.
Four other Scottish restaurants make it into the top 50 - The Peat Inn in Fife and the Edinburgh trio of Castle Terrace, Kitchin and Restaurant Martin Wishart.
The guide describes Fairlie as a "master technician" and gives the restaurant eight marks out of 10.
The restaurant - the only in Scotland with two Michelin stars - is said to use "unimpeachable ingredients" with "modern sensibility".
Guide editor Elizabeth Carter said: "Unimpeachable ingredients are at the heart of Fairlie's culinary endeavours, from the Gartmorn Farm duck served with ceps to the seasonal pickings from his flourishing two-acre garden (some 10 miles away).
"At the stoves, he's a master technician, eloquently schooled in the refined traditions of French haute cuisine, but applying a modern sensibility to dishes that always feel newly minted."
The Good Food Guide, owned by Waitrose, was first published in 1951 listing ''600 places throughout Britain where you can rely on a good meal at a reasonable price''.
Cumbrian restaurant L'Enclume was named the best in the UK for the fourth year in a row.
The 2017 guide awarded Simon Rogan's L'Enclume, in the village of Cartmel, a perfect 10.
Outside of the top 50 list there were mentions for Aizle in Edinburgh, Birlinn on Skye, Eusebi Deli in Glasgow and North Port in Perth.
Glasgow has almost doubled its number of entries in the guide this year, with 13.
Ms Carter said: "The redevelopment of the Finnieston dockyards and warehouses has helped to give a real boost to the Glaswegian dining scene, with many of the new venues offering a distinctly urban, modern approach, including stripped-back decor and small-plate concepts."
Singled out for praise in the longest serving category are Ubiquitous Chip in Glasgow - which has been featured in the guide for 45 years - Airds Hotel in Port Appin, Argyll, Ostlers Close in Cupar, Fife, The Three Chimneys on Skye, and Crannog in Fort William.