Adayar has won the 2021 Epsom Derby.
Richard Hannon’s big 50/1 outsider Mojo Star crossed the line a distant second, with Godolphin’s Hurricane Lane third.
Kirby was switched off Ed Dunlop’s 13-2 Derby contender John Leeper earlier this week in favour of Frankie Dettori, but shrugged off that disappointment to seal his maiden Classic win aboard Adayar, a son of the legendary Frankel.
Gear Up set the early gallop at Epsom, with Kirby on his heels on Adayar and Youth Spirit also prominent in the early stages.
Favourite Bolshoi Ballet was also towards the head of the field, settled in fourth on the outside, while John Leeper was restrained in last place by Dettori until the field reached Tattenham Corner.
Gear Up started to drop away with two furlongs to run, allowing Kirby a run up the inside rail and he soon put daylight between himself and the field.
Mojo Star finished well from off the pace to take second, with Hurricane Lane also keeping on at the one pace for minor honours, but Adayar prevailed by four and a half lengths.
Bolshoi Ballet and John Leeper were both ultimately well beaten and the result provided Kirby with a happy ending.
Oisin Murphy was booked for Adayar, but Kirby then replaced him on Thursday.
Kirby told ITV Racing: "There's been ups and downs, it's racing, but when it comes to Charlie Appleby, he's a top man. I can't thank him enough. He's a real gentleman and a great trainer."
Additional reporting by the Press Association.