Unbeaten in four heading to Keeneland, the son of Dubawi was one of two in the race for Appleby and had already proved his thirst for international competition with a pair of wins in Germany this season.
In his first visit to America, the one-time Belmont Stakes hope was given plenty of cover as the field embarked on three turns of the Kentucky turf and was posted wide as the field span the far turn and headed for home.
However, he stormed up the stretch once straightened up by James Doyle to put daylight between himself and Aidan O'Brien's Stone Age, who had been close to the pace throughout and went down valiantly in defeat.
Bill Mott's mare War Like Goddess fared best of the home contingent in third, with Mishriff a brave and respectable fourth from his outside draw in his final race.
For Appleby it was his third success at this year's meeting to equal the three he achieved in Del Mar 12 months ago and he was full of praise for both the winner and his winning jockey, who was striking at the Breeders' Cup for the first time.
He said: "This horse is well travelled, he's maturing and what he has done on turf has rejuvenated him and full credit for that goes to the team.
"I'm delighted to give James his first Breeders' Cup winner - I was confident he would get the job done and it was a great ride to wrap it up.
"I think this horse's style of running might not lend itself to Dubai and we will stick to turf with him."
Doyle added: "We went into the race with an open mind, we were a bit slowly away, but I was behind Nations Pride who took me into the race nicely.
"He was a little bit raw round the turns and I was relieved that there was more room for us in the straight.
"I think the faster ground also helped him. He was very relaxed having the pony with him, so relaxed it all took me by surprise to be honest."
Of Mishriff, John Gosden said: "He's been an extraordinary horse throughout lockdown, doing Derbys and Saudi Cups.
"Today he was stranded four wide and although we tried him with the blinkers they made no difference.
"I'm very proud to have had a horse like him who served us well right through to being a five-year-old."