McCarthy rejected a move to Fratton Park to join Rovers from FC Porto in the summer of 2006.
The South African striker fired in his eighth goal of the season to inspire Blackburn to the last eight.
McCarthy took advantage of some unusually slack Portsmouth defending to open the scoring after just 11 minutes.
Fellow countryman Aaron Mokoena drilled in a low cross for the unmarked McCarthy to take a touch and side-foot home past David James and into the bottom left-hand corner of the net.
Blackburn's injury woes took a turn for the worse 14 minutes later when Mokoena, in for Robbie Savage, was stretchered off with his left leg strapped up after suffering a serious looking knee injury.
Mark Hughes' misery was almost compounded five minutes before half-time when Pompey top-scorer Benjani raced clear only for Brad Friedel to perform a smart save with his legs.
Portsmouth boss Redknapp had clearly seen enough and brought on Matthew Taylor and £6million striker David Nugent at half-time to breathe fresh life into his flagging side.
Nugent should have equalised in the 55th minute when he produced a contender for miss of the season.
John Utaka whipped in a teasing right-wing cross to pick out Nugent unmarked at Blackburn's back post, but the misfiring frontman somehow headed wide from a yard out.
Nugent was almost made to pay for his howler nine minutes later when defender Christopher Samba came forward and smashed in a fierce volley which James managed to tip over with a brilliant reaction save.
Blackburn did not have to wait long for their deserved second goal though, which came 13 minutes from time when Morten Gamst Pedersen drilled home at the back post after Pompey had failed to deal with a David Dunn cross.
Substitute Kanu's stoppage-time header was scant consolation for a Pompey team eyeing a cup-run to end their 50-year wait for a major trophy.