White Noise pulled off the shock of the day in the Mares' Novices' Hurdle as the 40-1 shot powered over the line in first place.
Odds-on favourite Bambino Fever made a mistake when clearing a hurdle over the hill and failed to get back into contention.
Emotional jockey Tom Bellamy told ITV it marked a life's ambition fulfilled for him to ride a winner at Cheltenham.
Bellamy said: "I've waited my whole life for this day. I can't believe it, I'm speechless.
"I'm genuinely nearly crying here. I bunked off school to come and watch Cheltenham; now I can't believe I'm here."
McManus secured his first winner of the day in the Novices' Chase when 9-1 chance Meetmebythesea came home convincingly ahead of 25-1 shot Golden Dancer.
Trainer Ben Pauling told BBC Radio 5 Sports Extra: "He was good there today. He jumped very well.
"It looked like he had a bit left at the last. Hopefully, he has a bit to come.
"It means a lot to everyone, but training a winner here for one of the greatest men in the industry [McManus] means a lot to us. It is an important win."
Jack Kennedy rode short-priced favourite Wodhooh to victory in the Mares' Hurdle in what was trainer Gordon Elliott's first victory of this year's Festival.
Home By The Lee, a 33-1 outsider, won the Stayers' Hurdle from Ballyburn and Bob Olinger.
Trainer Joseph O'Brien told BBC Radio 5 Sports Extra that the horse is as "tough as nails".

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