More of That condemned Annie Power to her first ever defeat as Barry Geraghty's ride beat the Irish trained mare into second in the World Hurdle.
Four-time winner Big Buck's finished fifth and was retired immediately after the race.
Despite being billed as a two-horse race, it was Jonjo O'Neill's More of That who won from 15-2.
He beat 11-8 favourite Annie Power by a length for a fifth consecutive career win, with At Fisher's Cross third.
Eleven-year-old Big Buck's, who won this race every year from 2009 to 2012 before missing last season through injury, was never in the contest.
Commenting on his retirement, trainer Paul Nicholls said: "It's the obvious thing to do. I wouldn't ask him to run again - he's been a wonderful horse.
"Halfway round I could see he wasn't jumping so fluently and his legs weren't what they were.
"It's not an emotional decision - I'm delighted he's finished in one piece. It's the right decision at the right time and I'm thrilled. He's just been wonderful."
At Fishers Cross, with AP McCoy at the mount, made the first burst for home in the three miler before Annie Power, under Ruby Walsh, and Geraghty's More of That burst through.
But it was the latter who prevailed to follow up his Grade 2 win at the Osborne House Relkeel Hurdle in Cheltenham in December.
Victorious jockey Geraghty said: "He still is a little bit innocent but he's got an engine. I always felt I had the finish."
Willie Mullins, trainer of well backed Annie Power, conceded his horse was second best on the day.
"It was a good, fair race," he said. "I thought we jumped fantastically the whole way, but we were just beaten by a better horse on the day."
Earlier, McCoy claimed his first win of the Festival when he rode 7/1 shot Taquin De Seuil to the JLT Novices' Chase despite a back injury.
McCoy was limping before and after the race after falling on Goodwood Mirage on Thursday but the lure of become a winner was too much to pull out.
"It hurts a lot, I was up in the night, I was not sure if I would ride," he said.
"But I felt if I managed myself right I could get through it. However sore I feel now I would have felt a lot worse watching someone else win this."
The closest finish of the week came in the Pertempts Network Final as Fingal Bay beat Southfield Theatre after a lengthy photo-finish decision.
Tom Scudamore was a popular winner for 3-1 favourite in the Ryanair Chase as he burst through late with Dynaste, including a fine leap on the final fence.
Ballynagour gave Scudamore another victory in the Byrne Group Plate with the biggest win of the week by around seven lengths from McCoy's Colour Squadron.
Jockey Robbie McNamara rode 12-1 shot Spring Heeled to victory in the same race in which cousin JT McNamara was seriously injured last year.
JT suffered a fall in the Fulke Walwyn Kim Muir Challenge Cup which left him paralysed. He was thought to be following coverage of the race from a spinal injuries unit in Southport.