The 11-10 favourite beat Le Mercurey by three and a quarter lengths, with Bristol De Mai disappointing in third.
Tizzard, who also trains Thistlecrack and Cue Card, has three of the first four in the Gold Cup betting.
Ballyandy landed the Betfair Hurdle and Altior also won to cement his place as favourite for Cheltenham's Arkle Chase.
Aidan Coleman was a late call-up for Native River after regular jockey Richard Johnson pulled out because of illness.
But it was business as usual for the Hennessy Gold Cup and Welsh National winner, who is now 4-1 (from 9-2) for the Gold Cup behind 7-4 favourite Thistlecrack, with Cue Card and Djakadam at about 7-1
Coleman said of Native River: "He's just the perfect racehorse and (it was) very nice to have a sit on him and I wish them all the best for the future."
Paul Nicholls said his runner-up Le Mercurey had run well to get close to a horse he considers will win the Gold Cup on 17 March.
The champion trainer believes Le Mercurey will be a Grand National contender in the future, but will this year aim him at the Betway Bowl at Aintree.
Last year's Cheltenham Champion Bumper victor Ballyandy, trained by Nigel Twiston-Davies, won for the first time over hurdles as he beat Nicholls' Movewiththetimes.
Nicky Henderson's Altior coasted home by 13 lengths from Fox Norton in the Betfair Exchange Chase, registered as the Game Spirit Chase.
BBC racing correspondent Cornelius Lysaght
One of those days where it's hard to come up with a lead story but Altior's success in the old Game Spirit Chase probably shaded it.
Last season's Supreme Novices' Hurdle winner looks even more supreme this year, and this was the smoothest of performances, all the more meritorious because it came on unfavourably soft going.
He's rightly a hotter and hotter favourite for the Arkle (his pretty much certain target said Nicky Henderson), and he'll be a Festival banker for many. Native River's style is all about stamina and toughing it out, and he'll set a big test for all-comers in the Gold Cup.
Native River enhanced his Cheltenham Gold Cup credentials with a comfortable win for trainer Colin Tizzard in the Denman Chase at Newbury.