United made a sensational start, racing into a 2-0 lead inside the opening 10 minutes. Shea Lacey opened the scoring in the eighth minute before Mason Mount doubled the advantage two minutes later.
• Manchester United: Shea Lacey 8', Mason Mount 10'
• Brighton & Hove Albion: Charalampos Kostoulas 45+1', Pascal Groß 65', Maxim De Cuyper 69'
Brighton gradually recovered from their poor start and pulled a goal back deep into first-half stoppage time. Charalampos Kostoulas finished to give the visitors renewed hope heading into the interval.
The Seagulls then completed their comeback after the break. Pascal Groß equalised in the 65th minute, turning the pressure on United, before Maxim De Cuyper struck four minutes later to put Brighton 3-2 ahead.
United pushed for an equaliser during the closing stages but could not find a way past the Brighton defence. The defeat ended their Carabao Cup campaign at the first hurdle.
The collapse was particularly damaging because United had never lost at Old Trafford after leading by two goals in 50 years. Their previous defeat from such a position at home came against Tottenham Hotspur in September 1976.
The result also comes only three days after United's 1-0 Premier League defeat to Manchester City in the Manchester derby, leaving Michael Carrick's side with consecutive defeats.
For Brighton, the comeback secured progression to the fourth round and continued their impressive recent record at Old Trafford. The Seagulls showed considerable resilience after falling two goals behind and ultimately punished United's defensive lapses.
United must now turn their attention back to the Premier League, with Carrick and his players facing pressure to respond after a difficult run of results.