Brian Hernandez Jr piloted the four-year-old colt past the celebrated field by the first turn and stayed in front before holding off a late surge by Mucho Macho Man to win America's richest horse race in glorious late afternoon sunshine.
Mucho Macho Man, who almost pulled level while chasing Fort Larned hard down the stretch, finished half a length back in second with last year's beaten Classic favourite Flat Out a further six-and-a-half lengths adrift in third.
Game on Dude, who came desperately close to winning the 2011 Classic only to be run down by Drosselmeyer in the shadows of the post, finished a disappointing seventh out of 12 after making a slow start.
Fort Larned's jockey Hernandez struggled to keep a broad grin off his face after celebrating his first Breeders' cup win on his 27th birthday.
"It's the greatest birthday ever," he said. "I always had a lot of confidence in him (Fort Larned).
"(Trainer) Ian (Wilkes) and I talked about the race and he told me don't take him out of his game and let him do whatever he wants to do. He has a good cruising speed and I just let him go."
'Let go' by Fernandez from the off, Fort Larned never relinquished his grip on the race, leading all the way to earn Wilkes his first Breeders' Cup win as a trainer.
"We had to be there near the front and he was ready today," said Australia-born Wilkes. "He had galloped great over the track. I knew we were good when he broke sharp.
"That's where Brian (Hernandez) won the race. We broke sharp and Game On Dude broke bad. I trust Brian because the horse trusts Brian."
Fort Larned has now won eight of his 19 career starts, including five of nine this season, and emerged as a contender for the Classic after winning the graded Skip Away Stakes in March.
Jockey Mike Smith had been bidding to extend his record total of Breeders' Cup wins to 18 and came desperately close with his strong finish on board Mucho Macho Man.
"The other horse (Fort Larned) snuck away from me and I wasn't able to keep up with him at that point," Smith said of the closing stretch. "Brian has always been a great rider.
"He has great hands. I've known him since he started, and I knew he was going to win a race like this some time. I just wish it hadn't been today."
Game on Dude, trained by Bob Baffert who has won three Kentucky Derbies but is still chasing his first Classic winner, started the marquee race as the 6-5 favourite but never featured after his poor start.
"The first eighth of a mile cost him the race," said Baffert. "He wants to be right up there near the front and when he wasn't, that was it for him. It was unfortunate."
A consistent performer at the highest level, the five-year-old Game on Dude had won four of his previous six starts this season and had the perceived advantage on Saturday of running at his home track.