Alex Hughes hit a career-best 142 and Wayne Madsen (121) scored his 25th first-class century for Derbyshire as the visitors posted 460 on Day One at Bristol.
Not out overnight after a rain-affected first day, Hughes and Madsen added 233 for the third wicket, a Club record versus Gloucestershire, to help secure maximum batting bonus points and put their side in a good position.
Hardus Viljoen then claimed an early breakthrough before stumps leaving Gloucestershire on 47-1, trailing by 413 runs.
The two centurions started the day well, scoring quickly and both making half-centuries in seizing control of the session which saw Derbyshire add 89 runs for no loss.
Madsen reached 10,000 career first-class runs with a sweep for four and shortly afterwards flicked a four through fine leg to bring up his first century of the season.
Despite Gloucestershire taking the new ball, the runs kept flowing and Hughes soon reached his second century of the campaign, from 204 balls with 15 fours. The record stand eventually came to an end on 233 when Madsen was caught down the leg side by James Bracey for 121 and the score 307-3.
Matt Critchley (19) and Gary Wilson (5) were out either side of achieving a fourth batting bonus point as Derbyshire marched on after tea. Shortly after Hughes’ fine innings came to an end after surpassing his previous career-best, out to Kieran Noema-Barnett for 142 with Derbyshire 380-6.
Harry Podmore (43) and Harvey Hosein (37 not out) added a quick-fire 70-run stand as the visitors claimed all five batting points before wickets tumbled in search of quick runs. First, Podmore was caught, before Viljoen and Imran Tahir followed and Derbyshire were all out for 460.
Leading the attack with the ball, Viljoen had Chris Dent lbw in the fifth over for four, Derbyshire buoyed as the light began to fade at The Brightside Ground.
Benny Howell (33 not out) and Bracey (unbeaten on 5) looked to hit out as Derbyshire were forced to bowl spin at either end, but the hosts closed on 47-1, still trailing by 413 and needing 263 more to avoid the follow-on.
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