The Gunners have not won a major trophy in eight seasons, but Wenger has entrusted some of his fringe players to secure them passage to the next stage of the competition.
Home boss Gus Poyet, formerly of Arsenal's London rivals Chelsea and Tottenham Hotspur, names an attacking side for the clash at the Falmer Stadium.
New £2m signing Leonardo Ulloa is handed a debut alongside Ashley Barnes in a two-man Seagulls attack.
Reported Premier League target Liam Bridcutt and Will Buckley will aim to provide support from the flanks as Poyet makes four changes.
Casper Ankergren replaces Tomasz Kuszczak between the posts, while Andrea Orlandi, Vicente and Gary Dicker also drop out.
Arsenal: Szczesny; Jenkinson, Mertesacker, Koscielny, Santos; Diaby, Ramsey, Rosicky; Oxlade-Chamberlain, Podolski, Giroud
Brighton: Ankergren; El Abd, Greer, Calderon, Bridge; Bridcutt, Hammond, Lopez, Buckley; Ulloa, Barnes