Sussex captain Ben Brown hit 116 and David Wiese added 89 not out, as the hosts rallied after lunch to close Day One on 400-7 at The 1st Central County Ground.
Derbyshire took four early wickets, but the experienced Brown added 142 in partnership with Wiese as the hosts took control on the opening day.
All-rounder Sean Ervine made his debut on the South coast after signing on loan from Hampshire, while fast bowler Lockie Ferguson (2-95) also got his first taste of red ball cricket in a Derbyshire shirt.
After deciding to bowl first, there was an early change for the visitors as Harvey Hosein dislocated a finger in the warm-up, meaning Wayne Madsen took the gloves until Daryn Smit’s arrival, his introduction agreed by the captains and umpires.
Derbyshire bowled well under the cloud and claimed four Sussex wickets before lunch, including a first in the format for Ferguson.
Hardus Viljoen (2-93) got the breakthrough with the score 32-1 as Philip Salt was well-caught by Ervine for 15, before Ferguson had Tom Haines (8) caught by Critchley.
Luke Wells made 35, but stand-in wicketkeeper Madsen took a good low catch down the leg side to give Ravi Rampaul (1-51) his first wicket.
It was four before lunch to seal a good morning session for Derbyshire as Tony Palladino (2-45) picked up his first to leave the hosts 115-4 at the interval.
However, the second session belonged to Sussex and Brown as he added 103 with Harry Finch (82) and a further 57 with Wiese as Palladino claimed the visitors’ only wicket after lunch.
With fading light and Smit onto the field to take the gloves from Madsen, Derbyshire looked to capitalise in the final 32 overs and dismiss Sussex for a par score.
Rampaul left the field shortly after tea for a precautionary assessment at hospital after being troubled with breathing problems as the steadfast Brown marched on.
Soon Sussex went past 300 as the captain reached his century, but he fell after Derbyshire took the new ball, lbw to Ferguson in the 85th over.
Chris Jordan (3) was soon bowled by Viljoen as Derbyshire limited the damage late in the day, but Sussex will resume in the morning in a commanding position.
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