Taghrooda produced a powerful late surge to win the King George VI and Queen Elizabeth Diamond Stakes.
The 7-2 shot, ridden by Paul Hanagan, is the first filly to win the Ascot race in more than 30 years.
The three-year-old, unbeaten in four races, led favourite Telescope by three lengths, with Mukhadram third.
Taghrooda is only the second filly to win the Oaks and King George VI and Queen Elizabeth Stakes in the same year, after Pawneese in 1976.
Winning jockey Hanagan said: "It's such a buzz. It is something you never think would happen. The reception she got is just out of this world.
"She is so laid-back and that is tremendously important for a race like that."
|Recent winners of the King George VI And Queen Elizabeth Diamond Stakes|
|2014 Taghrooda||2010 Harbinger|
|2013 Novellist||2009 Conduit|
|2012 Danedream||2008 Duke of Marmalade|
|2011 Nathaniel||2007 Dylan Thomas|
Leitir Mor, the outsider of the eight-strong field, made the running until being overtaken on the home turn.
Hardwicke Stakes winner Telescope and Coral-Eclipse winner Mukhadram stole a march on the pack to lead into the final straight.
But Taghrooda, who was omitted from last weekend's Irish Oaks by owner Sheikh Hamdan bin Rashid Al Maktoum, surged past the pair to take the win.
Trainer John Gosden said: "It was a special performance and I'm very glad Sheikh Hamdan made the correct decision.
"I thought it was a bold and good plan. I thought it was a bit defensive going for the other race (Irish Oaks)."
"I'm absolutely thrilled and it was a great ride. I couldn't have been more pleased with her."