The John Gosden-trained five-year-old won last year but faced a tougher field this time and finished ahead of Dee Ex Bee and Master Of Reality
Stradivarius was priced at 11/8 at the start of the day but fell to evens at the off after Dettori won on A'Ali, Sangarius and Star Catcher ahead of the week's feature race.
"What an amazing horse he is. He got me out of trouble" said Dettori, who has won the feature race seven times. "He's the horse for the big occasion and people love him.
"It's great for everyone connected with the horse - every time he runs he delivers.
"I was half-thinking Capri was going best, then I changed my mind and followed Wayne Lordan, then I got the split and it was all over.
"He doesn't know how to lose and all I have to do is get him among the others and he does the rest. He is fantastic horse and he does the rest - and what a trainer."
Dee Ex Bee (7/2) led throughout but was no match for Stradivarius' late pace and finished just ahead of Master of Reality (66/1)
Gosden's star stayer enjoyed a faultless campaign in 2018 - winning the Yorkshire Cup, the Gold Cup, the Goodwood Cup and the Lonsdale Cup to land a £1m bonus through the inaugural Weatherbys Hamilton Stayers' Million.
Gosden, who had never trained a Gold Cup winner before Stradivarius won in 2018, paid tribute to the "mercurial" Dettori.
"Full marks to a remarkable horse and the sometimes mercurial, remarkable jockey - but I think it's all down to the horse, even though Frankie keeps saying it's him!
"When you think of Le Moss, Sagaro and Yeats they are wonderful horses and great for the public as people get to know them.
"He (Stradivarius) is a little guy with white socks and a white face, he looks like the milky bar kid should be riding him."
Dettori's wins saw the odds of his rides dramatically reduce throughout the day and bookmakers were braced for one of their biggest ever payouts if he delivers in the final two races.
In the penultimate race of the day, the 5:00 pm Britannia Stakes, Dettori's ride Turganev fell from 14/1 in the morning to 7/2 at the off. Dettori went early and gave it a good go in a crowded field as he chased a fifth consecutive win, but Biometric (28/1) was comfortably ahead.
"20 years ago I would have won that," Dettori said. "I love that it was 16/1 this morning but went as favourite. It wasn't to be. I've had a great day so I'm not going to cry"
Dettori had to settle for four wins after missing out in the last on Questionnaire as 22/1 South Pacific won the King George V Stakes.