Steven Alzate scored the game's only goal on 56 minutes as he bundled home following a Dan Burn cross past Liverpool's stand-in goalkeeper Caoimhin Kelleher, who was playing due to an illness for first choice Alisson.
Liverpool kicked off this match minutes after Premier League leaders Manchester City had beaten Burnley 2-0, which extended their lead over the reigning champions to seven points ahead of the meeting of the two sides on Sunday at Anfield.
Liverpool may have rediscovered their scoring touch away from home with eight goals in their last three matches, but their home struggles returned as Mohamed Salah was particularly wasteful.
Salah and Roberto Firmino both missed chances after Brighton's goal, while Kelleher was called into action in the Liverpool goal.
Liverpool's defeat to Burnley in their home match on Jan. 21 was their first Premier League loss at Anfield in 68 matches. This is the first time they have suffered back-to-back home reverses since September 2012.