The medium pace of Watkins and Cosgrove tore the visitors apart
Australian all-rounder Mark Cosgrove hit a match-winning 52, then did his stuff with the ball too as Glamorgan cruised home against Gloucestershire.
Cosgrove was backed by 43 from Jamie Dalrymple as Glamorgan piled up 166-6.
But the visitors collapsed from 38-0 to 72-9 as medium pacers Ryan Watkins (5-16) and Cosgrove (2-11) ran amok.
Only a last-wicket stand of 55 between Jon Lewis (30no) and last man Steve Kirby (25no) saved face as they were finally bowled out for 127.
Glamorgan, who threw away a great victory chance to lose by just one run against Somerset on Monday night, now go to Northampton on Friday night (1730 BST).
Gloucestershire are in local derby action at Taunton (1730 BST) against a Somerset side who have now won their first two matches.
Watkins' figures under the Cardiff lights were the best by a Glamorgan bowler in the eight summers of Twenty20 Cup cricket.
After Garnett Kruger had made the breakthrough by bowling William Porterfield for 25, Watkins did the damage in the sixth over, dismissing Alex Gidman, Craig Spearman and Chris Taylor (for a golden duck) in the space of four balls.
Earlier, Kirby had been forced out of the visiting attack by umpire Vanburn Holder after bowling two illegal beamers which meant newcomer Gemaal Hussain had to bowl the final five balls of the Glamorgan innings.
Ryan Watkins told BBC Wales: "It was great for the boys to get a win and to play my part as well.
"I'd had a word with our skipper Jamie Dalrymple and it was all about hitting a certain length and not being too full."
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