Yorkshire 200 for 3 (Lyth 92*, Tattersall 53*, Brook 44) beat Durham 156 for 4 (Stokes 90*, Brookes 3-21) by 44 runs
Yorkshire comfortably defended a 201 target against a Ben Stokes boosted Durham side at Emerald Headingley to make a winning start to this summer's Vitality Blast.
England all-rounder Stokes opened the batting in the chase and hit 90 not out off 68 balls in a 44-run defeat.
But all in all, this was a comparatively subdued return to competitive action following the left hamstring tear he sustained in training prior to England's Test against Pakistan here in early June.
Delighted Yorkshire coach Andrew Gale said: "Adam Lyth was the glue throughout the innings. I thought he played really well. But the two debutants were outstanding. Harry Brook and Jonny Tattersall showed us what they can do. "I thought we backed it up in the field. We set the tone early. We starved Ben Stokes of the strike, and you could see how frustrated he was when he came off."
Stokes was never going to bowl against a Vikings side who amassed 200 for 3 thanks to 94 not out from Adam Lyth and an unbeaten 53 from Jonny Tattersall, the pair sharing an unbroken 110 in 8.5 overs.
Stokes was tied down at the start of his innings, reaching four off 16 balls, but later accelerated without looking entirely comfortable, fitness wise. He reached 50 off 52 balls with a leg-side six and hit five in all.
"Ben keeps getting a ball in the [right] foot," Durham coach Jon Lewis said. "He got one there in the practice match he played on Tuesday, and he drilled one into his ankle in warm-ups before this game. It's just bruising. The hamstring, to the best of my knowledge, is not an issue.
"I think it was the running up and down which started to have an impact on what was already there. I think he's alright. He's certainly battled a bit and wasn't happy with himself at the end. He's not bowling yet fully, but I think he's ready as a batter."
The visitors slipped to 13 for 2 and failed to recover as Jack Brooks excelled with three for 21 during his first T20 appearance in three years. They finished on 156 for 4.
Although Yorkshire's innings was built around Lyth's effort, including nine fours and three sixes, it was lifted with the arrival of Tattersall at 90 for three in the 12th.
When he came in, Lyth had 39. By the time the left-hander reached his fifty, Tattersall had 37 as he found the gaps with plenty of innovation.
The Vikings wicketkeeper reached 50 off 26 balls with the penultimate ball of the innings.
The game started with Yorkshire, invited to bat first, losing Tom Kohler-Cadmore to a top-edged pull at Chris Rushworth in the second over as the score fell to nine for one.
Lyth then shared 81 in nine overs with Harry Brook, also on T20 debut like Tattersall.
Brook hit two sixes and four fours in a brisk 44 before was caught at long-on off Imran Tahir at the end of the eleventh over.
Gary Ballance then fell to Ryan Pringle at the start of the next over, superbly caught at cover by Tom Latham off a leading edge for a golden duck. But that was Durham's last success as the Lyth and Tattersall attacked.
Yorkshire started superbly with the ball as Brooks removed Graham Clark and Paul Collingwood in the space of three balls in the fourth over.
Clark was caught at deep mid-wicket and Collingwood lbw for a golden duck.
Although Stokes, who could play for England against India in Sunday's T20 at Bristol, warmed to his task, he never looked like getting the Jets home.
By the time he reached his fifty off 52 balls with a third six in the 15th over, Durham were 106 for four having lost Tom Latham and Will Smith to Steve Patterson and Brooks.
And it was very much stand and deliver stuff at the end from the 27-year-old.