With Sizing John out of the Gold Cup, it looks an extremely competitive renewal for the Timico Cheltenham Gold Cup.
Native River, ridden by leading jump jockey Richard Johnson, led throughout the $871,575 race at 3 5/16 miles to win by 4 1/2 lengths.
The success was at the hands of champion jockey Richard Johnson, who was landing the blue riband for the second time after Looks Like Trouble in 2000.
"Unreal, it's the race that everyone wants to win no matter what they might say", said Tizzard.
In an epic battle up the Prestbury Park hill, it looked for all the word like Nicky Henderson's charge would justify his favouritism but Native River (5/1) was not to be denied having finished third in this race previous year.
Native River produced a stunning front-running performance to win the Cheltenham Gold Cup and deny trainer Nicky Henderson a historic treble on Friday. They are two very fearless horses.
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The eight-year-old has not had the best of preparations, finishing fourth in the Irish Gold Cup after a jumping error and edged an enthralling encounter with Presenting Percy, victor of the RSA, in the Red Mills Chase at Gowran Park.
The master of Seven Barrows is on the cusp of becoming the first trainer to land the meet's three showpieces, having already watched Buveur D'air and Altior bring home the Champion Hurdle and Chase. "None of the others got close".
"His legs were gone", he said. "It was a tough steeplechase".
The pair are expected to resume their rivalry in next year's Gold Cup, with Native River already priced as a $6 favourite.
Native River had one start in the current season before Friday, a win in the Grade 2 Denman Chase at Newbury on February 10 against two rivals.