Similar to the first encounter, it was anything but a classic, but the South African's 87th-minute strike was worthy of winning any game, after Arsenal had seen two penalty appeals waved away.
The two sides arrived in Blackburn on the back of differing fortunes and it showed in the squad selection. Mark Hughes made just the one change to the side that strolled to a 3-0 victory at home to Portsmouth three days earlier, with captain Ryan Nelsen returning in place of Stephane Henchoz.
Arsene Wenger made five changes to the side that lost the Carling Cup final at the weekend, with Emmanuel Eboue, William Gallas, Gilberto Silva, Alex Hleb and Freddie Ljungberg all restored to the starting XI.
In a game when the first goal would always be crucial, it was almost inevitable that neither side would give much away in the opening exchanges - man of the match Chris Samba's shoulder barge on Julio 'The Beast' Baptista providing the most entertainment in the opening 20 minutes.
On 23 minutes, and after some neat interplay on the Arsenal right, Jeremie Aliadiere broke clean through on goal and went down under the challenge of Brad Friedel, but replays showed that the Frenchman left his legs trailing behind him and referee Graham Poll was right to ignore claims for a spot-kick.
Five minutes later and again the visitors felt hard done by when Ljungberg and Brett Emerton tangled on the edge of the box, only for the Hertfordshire official to wave play on.
Arsenal ought to have taken the lead just past the half-hour when Denilson's free-kick picked out the unmarked Baptista, but the Brazilian striker put his free header well over the bar.
Denilson was again the provider for the last chance of the half as Ljungberg was played clean through, but the Swede, who has missed much of the season through injury, let the ball escape him at the vital moment.
Rovers started the second half well and could have grabbed an unlikely lead just six minutes in when David Bentley, being watched by England coach Steve McClaren, supplied a brilliant ball across the face of goal, but Shabani Nonda somehow failed to connect.
Straight up the other end and Baptista forced a fine fingertip save from Friedel. But Rovers came back again and, following Tugay's quick free-kick, Bentley played in Morten Gamst Pedersen, but the Norwegian could only find the side-netting.
Just past the hour and both sides shuffled their packs, with Theo Walcott and Gael Clichy coming on for the visitors, while both David Dunn and McCarthy provided an extra attacking threat for the hosts.
And after Baptista again stung Friedel's gloves from fully 30 yards, it was the former FC Porto striker who quite literally smashed and grabbed the winner.
Collecting the ball wide on the left, McCarthy stepped inside Philippe Senderos before unleashing an unstoppable swerving shot past Manuel Almunia into the top right-hand corner from the edge of the box - his 16th and most important goal of the campaign.