The four-star hotel, which overlooks Central Station and underwent a £20million revamp in 2010, picked up the hospitality industry's top honour last night.
Judges praised the Grand Central's customer service, and business performance.
Hotel bosses also won praise for their "continuing investment", including a further expansion of the hotel and its champagne bar.
More than 500 hoteliers and guests attended the Scottish Hotel of the Year Awards, now in their tenth year, at the Crowne Plaza in Glasgow.
Gary McLean Quin, chairman of judges, said: "There were again many strong contenders for Scottish Hotel of the Year.
"But the Grand Central stood out because of its all-round performance, passionate leadership, staff management and wise future development."
A successful year also saw the Grand Central pick up the Events Hotel award.
The awards are based on thousands of guest feedback nominations, reviews by leading industry experts, travel writers, food critics and full-stay judging visits.
Glasgow's Jurys Inn picked up the Business Hotel award, and CitizenM, in the city centre, was named Budget Hotel of the Year.