Auguste Rodin triumphs as O'Brien wins the Derby again
Success came after the horse's hugely disappointing display when sent off favourite last month in another English Classics race, the 2,000 Guineas at Newmarket.
But 9-2 chance Auguste Rodin, ridden by Ryan Moore, returned to his best form at Epsom, overhauling 66-1 outsider King of Steel in the closing strides.
White Birch ran on for third with Artistic Star taking fourth.
"He (Auguste Rodin) came with a massive reputation but he's been stepping up all the time," O'Brien told ITV Sport. He's totally unique.
"He's so exciting for us and I'm grateful for all the team.
"Newmarket was one of those days when it all went wrong.
“As we all know, it's a funny game, it has to go round and everyone has to get their day. Sometimes you control the things you can control, but the variables that you can’t control all start falling against you and you can't stop that.
Moore added: "We didn’t go that quick, it turned in to a bit of a dash, but I was getting a nice smooth run...I always thought I had the race won, but I just had to get into him in the last furlong there and he responded very gamely."
'Only man that could do it'
Moore also hailed Irish trainer O'Brien's work in reviving Auguste Rodin's fortunes by saying of the trainer: "He's the only man that could do it.
"I've seen him get horses back. There's been horses that have run bad in the Guineas and have come back. Roderic O'Connor springs to mind and a few others, even Qualify ran bad in a Guineas and came and won an Oaks. Aidan can just do things."
The result meant jockey Frankie Dettori, riding Arrest, was denied victory in his final Derby before retirement.
There had been concerns the Derby, the premier race of the English flat season, would be targeted by animal rights activists and police did make two arrests during the race itself.
One man managed to jump the fence before being tackled and handcuffed by police on the racecourse while the crowd jeered and booed.
Minutes later, a woman attempted to climb the fence but was pulled to the floor by police.
The race itself, however, passed off without incident.
Earlier Saturday, police arrested 19 people ahead of the race after the rights group Animal Rising vowed to defy a court injunction and disrupt the blue-riband event.
Surrey Police reported the arrests in areas around the Epsom racecourse, near London, in the hours building up to one of British sport's highest-profile fixtures.
