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.

A gunman opened fire on a 33-year-old man in Dornoch Place, Bishopbriggs, at about 15:10 on Thursday.
The victim, who was collecting a child from St Helen's Primary, suffered non-life threatening injuries.
Detectives are treating the incident as attempted murder. Pupils were being offered support from social workers.
Officers said the gunman approached the victim, shot him and then ran off towards Ronaldsay Drive.
The suspect was holding a silver-coloured gun and wearing a high-visibility reflective yellow jacket with the hood pulled up.
He was described as being in his mid-40s, between 5ft 10in and 6ft tall and of heavy build.
Detectives said they were following a number of lines of inquiry.
They were keen to hear from anyone with information about a burnt-out grey Volkswagen Golf - registration FR12 PYB -  found nearby in Wood Lane which is believed to have been involved in the incident. It was reported stolen in March.
Det Supt Stevie Grant said: " I would appeal to anyone who has seen it either throughout the past few months or around the time of the incident to get in touch."
A major incident room had been set up at Kirkintilloch Police Office and extra patrols were being made to reassure the public.
The victim remains in hospital.
Ch Insp Craig Smith said: "Understandably people in the local community are shocked and alarmed at what happened and I believe a number of young children may have witnessed the incident.
"Police Scotland is working closely with our colleagues at East Dunbartonshire Council, and in particular the social work and education department, to ensure all those affected are provided with the best support possible."
Armed officers were called to the scene of the shooting, which happened as pupils were leaving St Helens at the end of the school day on Thursday.
One woman who lives in the residential area told BBC Scotland that she had heard three bangs which she believed were gunshots.
Several streets in the area were cordoned off, and access to the primary school was closed.
Native River enhanced his Cheltenham Gold Cup credentials with a comfortable win for trainer Colin Tizzard in the Denman Chase at Newbury.
[NEXT_CONCEPT]
Police investigating a shooting outside a primary school in East Dunbartonshire said a number of young children may have witnessed the incident.