The 3-1 favourite put a dismal run in the English 2,000 Guineas behind him to seal the Blue Riband, just as O'Brien's Auguste Rodin had done 12 months ago.
"It was hard to know what would happen today but we still thought we had the best horse. It just didn't happen in the Guineas," jockey Ryan Moore reported after partnering his fourth Derby winner.
City of Troy beat Ambiente Friendly (9-2) with another O'Brien runner Los Angeles (6-1) in third.
The result was the latest demonstration of O'Brien's magical ability to produce a horse for the big occasion.
Asked if this was the best of all his 10 Derby winners O'Brien told ITV: "No doubt."
City of Troy came in for a lot of criticism after the champion two-year-old in 2023 totally fluffed his lines in the Guineas, trailing in ninth of 11.
O'Brien though as he had done last year with Auguste Rodin stuck by his conviction that City of Troy still had all the qualities to add his name to the illustrious roll call of Derby winners.
"Ryan gave him an incredible ride," said O'Brien, before in typically modest fashion reeling off a string of names of people involved in City of Troy's preparation.
When he had caught his breath he said: "We knew the Guineas went totally wrong, he was too fresh, he blew up in the stalls.
"We knew the ability he had, he wasn't prepared properly, but since then he's been prepared beautifully.
"He has the cruising speed, and balance, just an incredible horse."
