Glenn Murray's 20th strike of the campaign after just 60 seconds, Tomer Hemed's chested goal and Uwe Huenemeier's first for the club completed a 3-1 victory with Che Adams pinching a consolation at the death.
Two of the home side's goals came in the second minute of each half, but Albion did not have it all their own way for much of the first period.
After taking the lead, the visitors actually looked the better side and provided promotion chasing Brighton with a few nervy moments as Lewis Dunk was forced off through illness.
An improved second-half display along with goals from Hemed and Huenemeier saw the Seagulls leapfrog Newcastle - who play Burton Albion on Tuesday night - at the top of the table.
It gives them a two-point lead over Rafa Benitez's side and ten advantage over third-placed Reading. Huddersfield dropped to fourth place ahead of their match with Norwich on Tuesday.
Albion made four changes as Bruno returned from injury and back into the starting XI with Gaetan Bong, Solly March and Tomer Hemed. They replaced Liam Rosenior and Seb Pocognoli, who dropped out of the squad, and Jiri Skalak and Chuba Akpom.
City also rang the changes with four from their 1-1 draw at Ipswich on Saturday with Stephen Gleeson, Clayton Donaldson, Che Adams and Cheick Keita all coming into the side.
It took just a minute for Albion to go ahead as a neat Murray touch allowed Beram Kayal to play a ball over the top for Anthony Knockaert. He drove into the box and slid in the overlapping Bruno, who superbly squared for the arriving Murray to guide the ball home in a lovely counter-attacking move.
The hosts came within millimeters of leveling in the eighth minute as Craig Gardener's free kick from 23 yards out crashed back off the bar with David Stockdale rooted to the spot.
And Albion weren't to learn their lesson as another soft free kick saw Gardener's low effort through bodies this time saved by Stockdale on 17 minutes.
Birmingham refused to lie down and hit Albion with a counter-attack of their own as Adams and Clayton Donaldson linked up well, before crucial blocks from Dunk and then Huenemeier.
Albion then suffered a blow as Dunk was forced out of the action on the half-hour mark through illness and was replaced by Fikayo Tomori.
The Seagulls started to get a foothold back in the game for the remainder of the half after weathering a Birmingham storm with the visitors looking sharp on the attack for the majority of the first half.
Chances had been few a far between at ex-Albion stopper Thomas Kuszczak's goal until Dale Stephens fizzed an effort over the bar in the 41st minute.
Albion then had penalty claims - albeit mainly from the crowd - waved away as Solly March went down as he tried to skip past Krystian Bielik on the stroke of half-time.
Within 90 seconds of the second half, March's dangerous cross was headed into a defender by Hemed and Knockaert's follow-up was blocked away.
But just a minute later, Albion did lead 2-0 as Bruno's cross was headed across the goalmouth by Murray and Hemed chested the ball in from a yard out.
It was 3-0 on 54 minutes as Birmingham fail to clear a Knockaert free kick and Hunemeier drove the ball home via a big deflection off Donaldson.
It was all about game management after that as Chris Hughton gave Stephens and Knockaert a breather. But despite a professional showing, Albion weren't able to register their fourth clean sheet in five matches as Adams' effort deflected off the chest of Huenemeier in the box and wrong-footed Stockade with six minutes remaining.
Brighton: Stockdale, Bruno, Huenemeier, Dunk (Tomori 31), Bong, Knockaert (Murphy 64), Stephens (Norwood 77), Kayal, March, Hemed, Murray. Unused subs: Skalak, Sidwell, Akpom, Manenpaa.
Birmingham: Kuszczak, Nsue, Bielik, Shotton, Grounds, Gardener (Frei 54), Tesche (Kieftenbeld 69), Gleeson, Keita, Adams, Donaldson (Maghoma 77). Unused subs: Jukiewicz, Dacres-Cogley, Davis, Legzdins.
Referee: Darren Bond.