The 66-year-old Briton, who had been at the helm since 1997 and was in charge of everything rules-related in the highly technical sport, suffered a pulmonary embolism, or blood clot.
“It is with immense sadness that I learned of Charlie’s sudden passing,” FIA president Jean Todt said in a statement.
“I have known Charlie Whiting for many years and he has been a great race director, a central and inimitable figure in Formula One who embodied the ethics and spirit of this fantastic sport,” he said.
“Formula 1 has lost a faithful friend and a charismatic ambassador in Charlie,” he added.
Whiting began his F1 career in 1977 working at the Hesketh team, then in the 1980s at Brabham.
He became an integral part of organising the world championship after joining the Federation Internationale de l’Automobile in 1988.
“We are shocked and saddened to hear of Charlie Whiting’s passing and our deepest condolences go out to his family, friends and colleagues,” Red Bull Racing tweeted as tributes began flowing.
Red Bull chief Christian Horner added that his death left “a huge void in our sport”.
“He was a man with great integrity who performed a difficult role in a balanced way,” he said.
“At heart, he was a racer with his origins stretching back to his time at Hesketh and the early days of Brabham,” Horner added.
“Charlie was a great man who will be sadly missed by the entire Formula 1 paddock and the wider motorsport community.”
The Haas team said the “entire motorsport community is in mourning”, while Renault called him “one of the pillars and leaders of the sport”.
“His drive to ensure exciting, safe and fair racing was unparalleled and his passion will be sorely missed,” Renault added.
Download our app and read this and other great stories on the move. Available for Android and iOS.