Albion's ten-match unbeaten run at Withdean came to an entertaining end against Second Division leaders Millwall.
Youngster Kevin Braniff celebrated his first start for the visitors with a brilliant strike in the 39th minute.
Paul Watson slammed the Seagulls level five minutes later from a free-kick, advanced ten yards into the Millwall area under the new law introduced this season.
Another unstoppable shot, this time by David Livermore, restored the Lions' lead on 53 minutes.
It leaves Albion with a mountain to climb in the second leg at the New Den on September 5.
Albion made one change to the team which came from behind to record their first victory at Withdean on Saturday.
The influential Cullip, suspended for the first two games following a red card at Shrewsbury at the end of last season, returned to the heart of the defence.
He replaced Darren Carr, who picked up a slight hamstring injury against Rochdale.
Jones, also banned for the opening two matches after his summer move from Southend, had to wait for his first start for the Seagulls.
He was among the substitutes, Mayo retaining his place at leftback.
Manager Micky Adams also stuck to his policy of naming a spare goalkeeper for Cup Ties, so Kuipers returned to the squad.
Millwall made a couple of changes to the side which made it two wins out of two in the Second Division by beating Notts County 4-3 on Saturday.
Paul Moody, who scored twice at Meadow Lane, was ruled out, so 17-year-old Eire Youth International Braniff came in for his debut upfront.
Bircham was preferred to Gilkes after replacing him and then snatching Millwall's late winner at Notts County.
The early exchanges were a bit scrappy, with no real pattern emerging, although Albion were the team asking most of the questions.
Mayo's long throw was headed clear by Dolan only as far as Carpenter just outside the area. The former Cardiff midfielder's shot was well struck and looked to be on target when it deflected off Ryan for a corner.
Leftback Ryan made a mess of a clearance moments later, but Freeman could only hook wide from an unkind angle.
There were a few optimistic appeals for a penalty when Watson played a free-kick into the feet of Hart, with his back to goal.
Hart, with Millwall captain Tuttle right behind him, went down, but referee Jordan rightly regarded the incident as innocuous.
Millwall began to find their rhythm and the prolific Harris prompted alarm with a pass for Livermore which defied Albion's offside trap.
Livermore just beat Cartwright as he rushed way outside his area, but when the ball broke to Braniff he rolled it into the side netting.
Cartwright required treatment but it was nothing serious and he was soon back on his feet.
Millwall came even closer to breaking the deadlock in the 13th minute. Canadian Bircham won possession and Reid's right foot shot from the edge of the area flashed the wrong side of the post.
The visitors threatened again through Cahill, scorer of both goals in their opening 2-0 victory against Reading.
The Australian midfielder finished a positive run with an angled left foot drive which the diving Cartwright did well to divert for a corner.
There was a blow for Millwall and a boost for Albion midway through the half when Harris, top scorer last season with 25 goals, had to go off.
Tyne came on for his debut, leaving the Lions with a rookie striker force.
An opportunity for Hart went begging on the half hour as a dinked cross from Watson caught the Millwall defence pushing up. Hart was left in space deep inside the area, but he failed to control the ball on his thigh.
A foul by Bircham on Oatway ten yards inside the Albion half angered Albion's captain. He reacted and suddenly several players from both sides were involved in a melee.
Referee Jordan took the heat out of the situation, taking both players to one side before showing each a yellow card. Zamora, with limited opportunities to demonstrate his scoring prowess by this stage, volleyed wide Mayo's resulting free-kick.
Cartwright came to Albion's rescue again in the 37th minute, blocking Livermore's effort with his legs after Braniff played him through.
Millwall took the lead six minutes from the break with a wonder goal by newcomer Brannif. Closely guarded by a couple of defenders just outside the area, he managed to make room for himself to curl a delightful right footer over Cartwright.
Hart almost equalised three minutes later. Latching on to a long ball through the middle, shrugged off Lawrence but could not keep his ensuing effort on target.
The Seagulls pulled level a minute before the break, with a little help from Tuttle. He was cautioned for kicking the ball away when Albion were awarded a free-kick.
The kick was then moved ten yards forward to inside the Millwall area under the new regulation introduced this season and Watson smashed it in with his trusty left foot.
Millwall regained the lead eight minutes into the second half with another stunning strike.
Crosby's poor clearance landed at the feet of Livermore. His angled left-footer, struck ferociously, fairly fizzed past the helpless Cartwright.
Albion's keeper almost blotted his copybook soon after with a misplaced clearance straight to Reid.
The Millwall midfielder's curling attempt from a wide position 25 yards out went inches wide of the vacant net as Cartwright raced back in vain.
Carpenter was hurt in the incident as he challenged Reid. He required treatment and was replaced in the middle of Albion's midfield soon after by Rogers.
Brooker tried to bring Albion level once more midway through the half.
The former Fulham winger finished a typically tricky run with a low shot which Warner held at his near post.
Zamora forced Warner into a fine point blank stop as Albion pressed for parity.
Cahill threatened to increase Millwall's lead with an elusive run and shot straight at Cartwright before Jones was introduced for his debut in place of Freeman 18 minutes from time.
Don't miss tomorrow's Argus for Seagulls Update
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