The final score was slightly flattering on the Premiership hosts who had been pushed all the way by their Division One opponents in a pulsating encounter.
Three late goals from Pompey gave the scoreline its emphatic look.
Substitute Quincy Owusu-Abeyie did the damage by scoring one and turning provider for two goals.
He broke the deadlock in the 66th minute, but the Saints hit back almost immediately through top scorer Rickie Lambert who restored parity.
But former Arsenal and Birmingham forward Owusu-Abeyie, who is on loan from Spartak Moscow, then set up Aruna Dindane for number two in the 75th minute.
With Southampton pressing forward for an equaliser, Pompey picked them off on the break.
Jamie O'Hara showed his class to release Nadir Belhadj to make it 3-1 with eight minutes to go and the on-loan Spurs midfielder then smashed in a fourth after Belhadj and Owusu-Abeyie combined.