The governing International Automobile Federation (FIA) said in a statement that the Briton, who started his career working for the Hesketh team in 1977, had died in Melbourne of a pulmonary embolism. He was 66.
Australian Michael Masi, a previous deputy race director of the local V8 Supercars series who has served as a steward at Formula One and Formula E, will replace Whiting for the Melbourne weekend.
"It is with immense sadness that I learned of Charlie's sudden passing," said Jean Todt, president of the International Automobile Federation.
"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. Formula One has lost a faithful friend and a charismatic ambassador in Charlie."
Whiting, who had been race director since 1997, started out with defunct British outfit Hesketh before crossing to Brabham to work with the sport's former commercial supremo Bernie Ecclestone in the 1980s.
A poacher turned gamekeeper, with a ready grin and self-deprecating sense of humour, he joined the FIA as a technical delegate in 1988.
Inside the paddock, he was known simply as Charlie -- the go-to man for teams, drivers and media.
At the FIA, Whiting was a driving force in pushing improved safety and played a key role in the introduction of the halo, the ring-like barrier fitted over the drivers' heads to protect them from heavy impacts and missiles.
The news was met with shock in the Formula One paddock.
"What he did for this sport, I mean, his commitment...he really was a pillar," five times world champion Lewis Hamilton told reporters.
"I spoke to him yesterday and walked the track for the first couple of corners together with him," added Ferrari's Sebastian Vettel. "Difficult to grasp when somebody is just not there anymore.
"He’s sort of been our man, the driver’s man. Obviously there are regulations and all that and then there is us and he was the middleman. He was someone you could ask anything of, anytime."
Former champions McLaren said Whiting would be remembered "as one of the giants of our sport, as well as a great colleague."
Ross Brawn, F1 managing director, said he was "devastated" to lose a friend and colleague.
"I have known Charlie for all of my racing life. We worked as mechanics together, became friends and spent so much time together at race tracks across the world," the former championship-winning boss of Brawn GP said in a statement.
"I was filled with immense sadness when I heard the tragic news."
(Additional reporting by Alan Baldwin in London, Editing by Peter Rutherford/Amlan Chakraborty)
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