Olivier Boscagli and Brajan Gruda gave the Seagulls a two-goal lead at the break, with poor defending costing the U’s dearly in the second half.
Further goals from Diego Gomez, a Stefanos Tzimas brace and Tommy Watson rounded off a miserable evening for United, who missed chances of their own, but were without doubt second best against superior opposition.
Gary Rowett made eight changes to the side which lost 1-0 at Birmingham City, with Sam Long, Brodie Spencer and Cameron Brannagan the three players to retain their place in the team. The Seagulls made 11 changes from the side which lost 2-0 at Everton on Sunday.
The Seagulls led 2-0 at the break, but United had a great chance inside the opening 30 seconds.
Przemyslaw Placheta though was unable to bring a bouncing ball under control, and Jason Steele was able to save from the winger inside the penalty area.
The Seagulls went straight up the other end, with Gruda feeding Diego Gomez, who burst through the middle and was then denied by Matt Ingram.
Gruda then seemed certain to score after 12 minutes, when he rounded Ingram inside the box, however Jack Currie made an incredible recovery challenge to get in the way of the effort.
The Seagulls though took the lead not long after, with a deflected effort from Boscagli looping in amid frustration from the U’s that a foul on Cameron Brannagan in the build-up wasn’t given.
Seven minutes after the opener, Joel Veltman played a pass over the top for Gruda to run onto, and the German expertly dummied Moore before firing past Ingram with aplomb.
Despite the ruthlessness of the Seagulls, United still posed a threat at the other end.
Stan Mills latched onto a loose ball and charged through the centre before seeing a shot from a tight angle saved at the near post from Steele.
Matt Phillips then swung in a deep cross from the right-hand side, and the backtracking Harris was able to flick it on for Placheta, who could only divert it off target.
Seven minutes before the break, Harris was presented with a glorious chance following a sloppy pass from Boscagli, but the striker only managed to fire straight at Steele from close to the penalty spot.
Spencer picked up a whack and was forced off nine minutes into the second half, with Louie Sibley coming on in his place.
That meant a defensive reshuffle as Sibley went to left wing back, with Currie tucking in as the left-sided centre back. Long switched to the right side of Moore in the three-man centre back unit.
The first goalmouth action of the second period saw Phillips produce a good block to divert a Ferdi Kadioglu shot out for a corner which came to nothing. A Kadioglu effort from 20 yards then went into a crowd of bodies and behind for a corner.
From that set piece, Gomez scrambled in from close range to make it three for the Seagulls.
Rowett made a triple change midway through the second half, with one of those – debutant Nik Prelec – chasing a ball over the top before being denied by a good save from Steele.
The Seagulls again displayed a Premier League level of ruthlessness by adding their fourth goal of the tie, as Tzimas ran through the centre and finished low into the bottom corner past Ingram.
Tzimas made it a brace six minutes later when he took full advantage of a sloppy ball pass and found the back of the net.
The U’s had three chances within the space of a matter of seconds inside the final 10 minutes, but Steele superbly saved from Luke Harris and Prelec, with Brian De Keersmaecker then seeing a third attempt blocked on the goal line.
Watson, on as a substitute, added a sixth for the Seagulls from inside the box following more sloppy play from United.
[Oxford United](http://www.thisisunited.com/) (3-4-3): Ingram; Spencer (Sibley 54), Moore, Long; Phillips (L Harris 66), Vaulks, Brannagan (De Keersmaecker 66), Currie; Mills, M Harris (Bradshaw 83), Placheta (Prelec 66).
Unused subs: Cumming, ter Avest, Goodrham, Snowden.
Booked: Mills.
Brighton & Hove Albion (4-2-3-1): Steele; Veltman (Tasker 78), Coppola, Boscagli, Igor Julio; Milner (Kostoulas 78), Hinshelwood (Baleba 66); Howell, Gomez (Tzimas 66), Kadioglu (Watson 66); Gruda.
Unused subs: McGill, Lamptey, O’Riley, Simmonds.
Booked: None.
Referee: Oliver Langford (West Midlands)
Attendance: TBC (TBC visitors)