The 21-year-old midfielder, who teamed up with Ralph Hasenhuttl’s men in the summer from Belgian First Division club Standard Liege, made his second appearance for the Saints and impressed.
30 minutes into the encounter, Brighton were reduced to 10-men after Florin Andone received a red card for serious foul play.
Southampton then capitalised on their numerical advantage with Djenepo opening the scoring one minute after replacing Yann Valery in the 54th minute.
Morocco international Sofiane Boufal then set up Nathan Redmond to seal the victory for the St Mary's Stadium outfit.
The win propelled the Saints off the bottom-three to 17th spot on the table with three points from three games.
The Mali international will hope to make his first start for Southampton when they square off with Fulham in Tuesday's League Cup tie.