Durham U15s succumbed to a 30-run defeat in the ECB County Cup Group 1B clash.
Derbyshire made a daunting 230-7, with Max Webber (80) and Nils Priestley (56) stealing the show, while Matthew Oswell bagged 2-47.
Josh Clifford, Aaron Feroz, Dean Storey, Sam North and Jonny Bushnell also struck for Durham.
In reply, Durham had a good go, with eight batsman getting to double figures although no-one could make a match-changing knock.
Sol Bell (35), Matthew Brown (25), Adam Khan (20) and Patrick Cooper (19) led the way as Durham fell short on 200 all out as James Hall grabbed 3-38.