For 70-year-old Harrington it was her 10th Festival victor and added Gold Cup success to the Champion Hurdle and the Queen Mother Champion Chase while for Power it comes 10 years after he won the Grand National on Silver Birch.
Djakadam, bidding to give Willie Mullins his seventh Festival victor, set sail for the judge in front but had nothing left to give in the closing stages and finished fourth.
As many as nine horses were in with a winning chance on the home turn, out of the field of 13, but Sizing John (7/1) was able to use his two mile pace to quicken ahead at the last.
Native River (7-2) was a short-head away in third and Djakadam - twice the runner-up - was fourth.
At the other end of the career spectrum is his stablemate Native River.
The Aintree Grand National-winning jockey was sidelined for a couple of weeks at the end of January with a ruptured disc in his back while he was also wearing protective gear until recently for an eye injury he sustained a year ago. He had the ideal prep when winning Newbury in February and 26% pf all stakes through the site have been on the proven stayer.
"It's absolutely fantastic. My first runner in a Gold Cup", Harrington said.
But poor Lizzie Kelly, having her first ride in the Gold Cup got no further than the second fence on Tea For Two.
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A mighty leap from the eventual victor at the second-last effectively sealed his fate, and the 7-year-old quickly went three lengths up on his pursuers, staying on strongly to give owners Alan and Ann Potts a longed-for success in steeplechasing's blue riband.
"This is quite unbelievable", exclaimed former three-day eventer Harrington, the most successful female trainer in the history of the Cheltenham Festival, whose previous stable stars include Champion Hurdle victor Jezki (Ire) (Milan ) and Champion Chaser Moscow Flyer (Ire) (Moscow Society).
With Sizing John she has completed the triple crown of Cheltenham's great championship races, and typically she instinctively handed the credit to Power.
But he and jockey Ruby Walsh had a golden afternoon yesterday, picking up four race wins.
She paid tribute to Henry de Bromhead, who trained Sizing John before owners Alan and Ann Potts chose to move their entire stock - including Fellow Festival victor Supasundae - elsewhere previous year.
"I can't believe it, I've got to get a Classic now (on the Flat)!"
Owner Alan Potts names his horses after the mining term "sizing", which means to extract minerals by crushing. Since the first day I rode him behind Douvan, I felt that all he did was stay. Taquin du Seuil (Fr), who was second in the Coral Cup on Wednesday, was bred by Marc.