The Falcons won by 55 runs in West Yorkshire.
Derbyshire defended an imposing 208 target at Emerald Headingley to secure the Vitality Blast double over Yorkshire for the third successive season, winning by 55 runs.
The Falcons were fired to 207 for five by superb fifties for Leus du Plooy and Wayne Madsen, who shared a damaging third-wicket partnership of 87 in seven overs to advance from 55 for two in the seventh.
Both hit fifties - du Plooy with 51 off just 23 balls and Madsen 66 off 37.
Overseas fast bowler Logan van Beek then starred with four for 17 in three overs as Yorkshire, for whom Jack Leaning top-scored with 36, were bowled out for 152 with 17 balls remaining.
The Falcons were bottom of the North Group coming into this clash, but won for the third time in eight to leapfrog a Vikings side who have now lost four in nine and only won once.
Derbyshire, having been inserted, were given a brisk start by captain Billy Godleman, whose 16-ball 28 included two of 11 sixes in the innings.
Du Plooy and Madsen hit four apiece in their explosive, game-changing third-wicket stand.
Left-hander du Plooy targeted the short leg-side boundary towards the East Stand side from the Kirkstall Lane End.
He hoisted fledgling left-spinner Jack Shutt, who had dropped a tough chance at third-man with Madsen on 28, over mid-wicket on the way to Derbyshire’s joint fastest fifty in any format.
In 2015, Wes Durston also hit a 20-ball fifty, and he was present on the ground as part of the Loughborough Lightning coaching staff. They had played a morning women’s Super League match.
The Falcons innings, however, was given real impetus when 45 came off the 12th and 13th overs combined, taking the score to 141 for two.
Du Plooy hit the lion’s share of 32 off compatriot and former international quick Duanne Olivier in the 12th.
He hit the first ball of the over, a no ball, for a straight six before depositing the free hit over wide long-on and out of the ground. A further six and two fours came off the rest of the over.
Typically inventive Madsen reached his fifty off 31 balls shortly afterwards, but both fell lbw to David Willey and Tim Bresnan as the score reached 179 for four in the 17th.
Yorkshire actually dragged things back in the last five overs from 162 for three.
Bresnan, who had only bowled two overs in three previous Blast appearances this year, struck twice in the 17th to remove Madsen and Matt Critchley - caught at cover - on the way to two for 17 from two overs.
Yorkshire’s chase was subject to an early blow when captain Tom Kohler-Cadmore was caught at point off van Beek’s third ball.
Adam Lyth (28) and Willey both hit sixes to take the score beyond 30 in the third over, only for the latter to slice van Beek to third-man as the score fell to 31 for two.
Lyth was then caught behind off Ravi Rampaul, Jonny Tattersall was lbw reverse sweeping at Critchley’s leg-spin and Bresnan was run out (89 for five in the 10th).
The Vikings remained afloat - just - as Jack Leaning and Jordan Thompson both struck sixes and shared 45 in four overs.
But when both fell in the 14th to van Beek, Thompson (23) caught at cover and Leaning brilliantly caught behind by a diving Daryn Smit off the glove for 36, Yorkshire were done for at 137 for seven.
Luis Reece then struck twice in the 18th over to help mop up the tail before a second run out.