Wayne Madsen and David Wainwright hit career-best scores, but Ashwell Prince helped guide Lancashire Lightning to victory.
An 80-run partnership between Madsen (78) and Wainwright (40) helped the Falcons recover from a slow start to post 190-9 from their allotted overs.
But the hosts made a rapid start in response thanks to Stephen Moore (34), before South Africa international Prince (80 not out) steered Lancashire to a six-wicket win in the 36th over.
After winning the toss, the Falcons lost both openers in quick succession to be reduced to 27-2 in the eighth over.
Paul Borrington – who hit a career-best 72 against Surrey on Sunday – and Madsen begun the Derbyshire fightback, adding 27 runs in seven overs before Borrington was bowled by Arron Lilley (4-30).
Off-spinner Lilley also removed Ben Slater (5) – who was making his List A debut for Derbyshire – Alex Hughes (11) and Tom Poynton (0) during his seven-over spell to halt Derbyshire's progress and leave Karl Krikken’s side in a spot of bother on 92-6.
The terrific partnership between Madsen and Wainwright, however, helped the Falcons recover from a precarious position to close on 190-9.
Captain Madsen led the way hitting five fours and a six in his 92-ball vigil, before the skipper was finally dismissed for a career-best List A score of 78.
Wainwright continued where his Captain left off taking the attack to the Lancashire bowlers during the final overs. The all-rounder struck three fours in his knock of 40 off 39 balls, his highest List A score, to help the visitors post a competitive total.
Lancashire made a quick start courtesy of the explosive Stephen Moore. The 32-year-old hit six fours in his eye-catching 32-ball innings, before he was clean bowled by Wes Durston for 34.
Tom Smith (26), Simon Katich (15) and Steven Croft (14), however, all made useful contributions as Prince led Lancashire serenely towards their victory target. And it was left to 22-year-old Jordan Clark (18 not out) to seal victory in the 36th over.
Durston was the pick of the bowlers for Derbyshire, returning figures of 2-31 from his eight overs, while Madsen (1-11) and Tim Groenewald (1-36) picked up a wicket apiece.
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