Albion suffered their fourth straight defeat against the First Division leaders in a compelling and fluctuating South Coast derby.
The Seagulls came from behind early on to rock Harry Redknapp's star-studied Pompey by taking the lead after 19 minutes.
But it all went wrong after that for Martin Hinshelwood's men and his two new signings.
Centre half Guy Butters conceded a pivotal 26th minute penalty against his old club.
Loan striker Graham Barrett from Arsenal was sent off on his debut on 76 minutes after scuffling with Matthew Taylor.
A sell-out crowd of 19,031 at Fratton Park saw Albion fall behind to a strike by the impressive Taylor in the third minute.
Captain Danny Cullip slotted the Seagulls level on eight minutes after Barrett had a shot blocked, then Paul Brooker latched on to a back pass by Richard Hughes to put them ahead 11 minutes later.
Portsmouth were rattled until former Gillingham stopper Butters was penalised for holding Deon Burton.
Paul Merson equalised from the spot and Stetoslav Todorov restored Portsmouth's advantage in the final minute of the first half.
A cracker from Jason Crowe on 52 minutes made sure Pompey equalled their best ever start to a season.
Albion's agony was compounded by the hardworking Barrett's red card, which leaves him facing a three-match ban.
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