The 5-4 shot, trained by John Gosden, saw off the challenge of 9-1 Ulysses in second, with 8-1 Idaho in third.
Racing against older horses, the three-year-old added to her Oaks success at Epsom and in Ireland this year.
Last year's winner Highland Reel  - Idaho's brother, priced at 5-1 - finished in fourth place.
Under rainy and overcast Berkshire skies, Enable impressed as she raced away from the four-year-old Eclipse Stakes winner Ulysses.
The summer event attracts some of the best horses from across the world, with this year's line-up for the mile and a half race proving no different.
Previous Group One winners Jack Hobbs, My Dream Boat and Ulysses were joined by Sixties Song, the latter travelling from Argentina.
Detorri had been on an intense diet to achieve the 8st 7lb weight required to ride a three-year-old filly in the event.
"All the days injured, this last week not eating, it was well worth it," the 46-year-old Italian told BBC Sport.
"It means a lot to me. I missed Royal Ascot to come back here, having pushed myself to extremes to get back.
"My fifth King George, what a buzz. I can't wait to have something to eat and a glass of champagne. I think I deserve it now."
Trainer Gosden told ITV Sport: "Enable is as good a filly as I have ever trained."
BBC Sport horse racing correspondent Cornelius Lysaght
Enable was magnificent, showing herself to be a filly - and indeed a three-year-old - of the highest calibre as she swept aside talented, and mainly older, rivals headed by the admirable Ulysses.
It was an electric turn of foot that Enable demonstrated with still over a quarter-mile to go before becoming the first filly to complete the Epsom Oaks-Irish Oaks-King George treble.
Frankie Dettori continues to shine for his sport, even on this most dismal of wet days. Having lost seven pounds in seven days to make the weight, he fully deserves the big dinner, plus a glass of champagne, he said he craves.
Dual Oaks winner and race favourite Enable, ridden by Frankie Dettori, has won the prestigious King George VI and Queen Elizabeth Stakes at Ascot.