The 6-4 favourite gave the Ballydoyle-based trainer his sixth win in the Classic.
Fifth home in the English equivalent earlier in the month, the Johnny Murtagh-ridden grey hit the front two furlongs out.
And he powered clear in the testing ground to see off the previously unbeaten 5-1 shot Rayeni by 4½ lengths.
Richard Hannon's Soul City ran well to finish third but Newmarket runner-up Delegator disappointed, failing to act in the mud.
O'Brien, who has a strong hand for the Derby at Epsom in a fortnight said: "All the horses have improved for their first run and since Newmarket the horses have really started coming.
"We've been happy with Mastercraftsman at home. He is a great traveller and he can quicken."
Murtagh added: "He's a very good horse, very brave and tenacious. He has the heart and will to win which all good horses have."
At Haydock, Sir Michael Stoute's Desert Creek justified 5-4 favouritism in the Betfred Silver Bowl.
Backed in from 5-2 in the morning, he worried supporters early on running freely under Louis-Philippe Beuzelin. But he stayed on when he kicked for home two furlongs out and held off Set The Trend.
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