Vintage Clouds provided the first shock of the Festival, with a 28-1 victory in the Ultima Handicap Chase.
Sue Smith's grey, ridden by the Yorkshire yard’s Grand National-winning jockey Ryan Mania, was running in the opening handicap of the meeting for the fifth year in succession.
The 11-year-old’s best previous effort was second in 2019 – but this time, he took over on the final circuit and was never headed again.
Runner-up Happygolucky, the 100-30 favourite, and third-placed Aye Right both ran with great credit but never looked like pegging back the winner, beaten five and a half and a further two and a quarter lengths respectively.
After being told he is a 'Cheltenham Festival winner', Mania said: "I’ll be honest, I never ever thought I’d hear those words mentioned.
"It’s been a long road back. Everyone knows I took nearly five years out of the game – and to come back to Cheltenham, I was lucky to get rides, let alone winners.
"This horse has been a real stalwart on the yard. He needed a wind op, and the cheekpieces have helped. It’s unreal.
"He was loving it the whole way round. We missed at the last down the back, and I just gave him a squeeze and he came back underneath me. I knew then that I’d be on the bridle at the end – but never did I think he’d storm up the hill like he did."
"About 18 months after the Grand National I was in a dark space and I saw no way out other than to walk away from the sport I love. I was enticed back with unfinished business being the main reason. Luckily it’s all gone really well."
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Jeff Kidder delivered a huge shock, and a fourth victory on Tuesday's card for Ireland, with an 80-1 success in the Boodles Juvenile Handicap Hurdle.
Sean Flanagan delivered Jeff Kidder with a strong challenge to lead on the run-in and beat Saint Sam, the 9-2 favourite, by two lengths.
Elham Valley (66-1) was half a length back in third with Houx Gris (11-2) fourth, a further one and a quarter lengths away.
Flanagan, who was riding his first Festival winner, said: "He's come here in a good vein of form. His form at home hadn’t been the most solid and his last run at Leopardstown was his first run after a bit of a lay-off and we kind of used it for experience more than anything else.
"When we got levelled out into the straight I knew he was going to stay well and he’s jumped well on the whole.
"I’m delighted for Noel and all the team at home. If it wasn’t for Noel, I wouldn’t be here – you need the horses and the staff and everything.
"To be fair to Noel said after a bit of work last week that this horse had a right chance and when he says something like that you stand up and take note. To be fair, he was right.
"I genuinely said when I passed the line, 'I can’t believe it’. I was talking to a few of the lads who have ridden here and they said it’s a feeling you can’t explain.
"Even though there’s no crowds here, it was brilliant – I can only imagine what it would have been like if there was (a crowd)."
Meade said: "I thought he had a chance. He worked the other day and I was very happy with what I saw. I said to Sean you’ve got two good rides at Cheltenham for me this week and I think you will be thereabouts on this one.
"He is a stayer on the Flat and that’s what you need around Cheltenham. That is what he ended up doing, just outstaying them. I think the better ground helped as well.
"Colin Keane has been riding him on the Flat and he said he will win you a Cesarewitch one day and hopefully he is right.
"He will run on the Flat again, but we will look at another race over hurdles and we might go to Punchestown with him."
Galvin, formerly with Gordon Elliott before being transferred last week to Ian Ferguson's yard in Northern Ireland, was a gritty but decisive winner of the closing Sam Vestey National Hunt Challenge Cup Novices’ Chase.
In a race usually confined to amateur riders but this year exclusively for professionals – while their counterparts remain subject to suspension under coronavirus restrictions – Jack Kennedy doubled his tally for the meeting.
He had 7-2 shot Galvin in contention throughout, but behind the leaders in this marathon contest, until taking closer order into the straight and jumping to the front at the last to beat Next Destination by a length and a half.
Foster’s Escaria Ten was the same distance back in third.