England batter Jordan Cox scored a fine unbeaten 86 off 29 balls - hitting 10 sixes - as the Invincibles bettered Manchester Originals' score of 5-208, set against Northern Superchargers three years ago.
Invincibles opening pair Tawanda Muyeye (33) and Will Jacks (38) laid the foundations in the 25-ball powerplay.
Cox then delighted the home support by smashing four sixes off Ajeet Singh Dale, who was making his Hundred debut. Sam Curran added a swift 34 off 19, with back-to-back sixes and four boundaries.
Welsh Fire saw Stephen Eskinazi caught off the first ball of their reply from Australian Jason Behrendorff.
Although Jonny Bairstow set about making a solid 50 and Tom Kohler-Cadmore added 31 from 16, it never looked like being enough.
The Fire could only make 143 all out, as Tom Curran finished with four wickets from his 15 balls and Behrendorff took three.
In the day's other Hundred fixture, Australia's Marcus Stoinis smashed a six to complete Trent Rockets' four-wicket defeat of Southern Brave.
Chasing 141 to win, a six from Stoinis, who finished on seven, took them to 6-145 with four balls remaining. Stoinis had earlier taken 2-18.
Rockets suffered a blow when batter Adam Hose earlier suffered a serious ankle injury.
Hose was taken to hospital after dislocating his right ankle in the field - an incident that resulted in the match being paused for 10 minutes.
A batter down in Hose's absence, the Rockets then slipped to 4-60 in their chase with Joe Root out for six.
But Tom Moores hit 55 from 30 balls and Tom Banton fell one short of a half-century before Stoinis finished the job as the Rockets kept pace with the front runners.
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