Harrington, 71, admitted being very nervous before the one-mile Group One for three-year-old fillies, despite being used to success at the very top over jumps in races such as the Cheltenham Gold Cup, Champion Hurdle and Queen Mother Champion Chase.
Unlucky in the Albany Stakes last year, Alpha Centauri (11-4 favourite) made amends in style.
Winner of the Irish 1,000 Guineas, she left a strong field that included the victors of the English and French equivalents, Billesdon Brook and Teppal, trailing in her wake.
They were nowhere to be seen as Colm O’Donoghue simply guided his mount home by six majestic lengths from Threading, with Veracious third.
“I’m relieved. I got very wound up. I was very nervous today - I know she’s very good,” said Harrington. “It was nice going into the Irish Guineas very much under the radar. She hadn’t run well on soft ground before that.
“I had confidence in her. She wants good ground, I don’t think she goes on heavy ground.
“Today was different. She was favourite and we were there to be shot at.”
She added: “I have a lot of people behind me and a lot of very nice owners who give me nice horses.
“I’ve had Ascot winners, but I’ve never had a Royal Ascot winner and it’s absolutely fantastic.”
Alan Cooper, racing manager for owners the Niarchos family, said: “We were nervous going into the race, not quite knowing where we stood in the links with the form, but we found out today.
“Jessie’s record speaks for itself. I saw the filly on Saturday and everything was wonderful. I’ll have to talk to Jessie and to the owners, but there is a race in Deauville in the middle of August, the Jacques le Marois, which the family sponsors. We might have to consider that.”
Michael Stoute’s record-breaking exploits got better when he took the Commonwealth Cup with Eqtidaar (12-1), who held Sands Of Mali by half a length in the hands of Jim Crowley.
Having become the winning-most trainer at Royal Ascot, the Newmarket handler enjoyed his third success of the week in a race that was only inaugurated in 2015 and had previously eluded him.
“We’ve always liked this horse,” he said. “When he ran here in the Pavilion it didn’t go quite right for him and at Newbury (last time) he was on the wrong side of the track and at halfway he was beaten.
“He worked very well the other week with Jim Crowley, so we were hopeful.
“He’s progressing nicely.”
Charlie Appleby feels Old Persian (9-2) is a horse for the future after the son of Dubawi won the ‘Ascot Derby’, the King Edward VII Stakes.
“I was so pleased half a mile out with the way he was travelling and once this horse hit the front I was confident he would see it out well given the pace they had gone,” said Appleby.
He’s a typical son of Dubawi - he’s improved from two to three and I’m sure he will progress from three to four.