Trainer Oliver Sherwood paid tribute to the horse whose death was met by stunned silence in the paddock.
He told the BBC: 'I always said he'd die for you, and he has today, doing what he loved most.
'He wanted to win that race, by God he wanted to win it -- he was beat at the last and he fought the last 50 yards to get up and win.
'I've trained for 32 years now and horses like that don't come along very often.'
Many Clouds was bought for €6,000 in 2007 and, since then, has won more than £900,000 in prize money.
He has won 12 of his 27 races and was ridden by Aspell in every one.
Viewers took to Twitter to express their grief and admiration for the champion racehorse.
One user said: 'Terrible scenes here at Cheltenham. Many Clouds has just beaten the best horse in racing and collapsed.'
Another added: 'Terrible, terrible news. Absolutely gutted.'
Luke Stevens wrote: 'Can't even cope with that news. Let's just take a moment to actually realise what this horse has achieved.'
Others took to social media to condemn the sport as 'animal cruelty'.
Mike Piper wrote: A horse - Many Clouds - just died after winning a race. This. Is. Animal. Cruelty. I'm not a hunt saboteur, I'm not an animal rights activist.
'I'm a human being who doesn't like the idea of animals dying for our entertainment. Ban it.'
Another Twitter user added: 'Horse ridden to death. Time to end the cruelty of horse racing.'