McCarthy changed all 11 of his players from Saturday's win over Fulham to take on a side 82 league places beneath them - and two goals from Sylvan Ebanks-Blake, Nenad Milijas' classy free-kick and a late Sam Vokes strike vindicated his decision at Sixfields on Tuesday night.
The Cobblers are tricky customers in the cups, having beaten Roy Hodgson's Liverpool on penalties at Anfield last season and seen off Championship Ipswich in the first round earlier this month.
But there was to be no repeat after Adebayo Akinfenwa squandered a gilt-edged chance to put them ahead when he blazed over from three yards out.
Lewis Young, the young winger attempting to follow in the footsteps of his famous big brother, Manchester United and England star Ashley, showed glimpses of his potential.
But Wolves rarely looked troubled after Ebanks-Blake fired them ahead.
The striker should have given them an eighth-minute lead when Michael Kightly's through-ball sent him clean through on goal but Cobblers keeper Sam Walker stood up well and got a vital touch on the shot.
And Town blew up their big opportunity to take a shock lead after 14 minutes when Kelvin Langmead headed on Ben Tozer's throw-in and the portly Akinfenwa scooped the ball over the crossbar.
The underdogs knew they could not afford to squander chances like that, especially with Wolves beginning to warm to their task.
Ebanks-Blake had already flashed a fierce shot across Walker's goal, and when the ball fell to him in exactly the same spot after 31 minutes he made no mistake.
Debutant Jamie Reckord, who had a spell on loan with Northampton last season, floated in a diagonal cross which Ebanks-Blake chested down in the right-hand corner of the area before rifling his low shot past Walker and into the net.
Ebanks-Blake could have made it two when he rounded Walker but the angle was too acute and he rolled his shot wide.
But the second goal did arrive with eight minutes of the first half remaining, and a superb strike it was too.
Arron Davies fouled Adam Hammill some 25 yards out and Milijas stepped up to curl his free-kick into the top corner as Walker stood and admired.
As first-half stoppage time approached Town almost pulled one back when Jake Robinson crossed for Young but Dorus De Vries, making his debut, saved well at his near post.
Northampton, to their credit, continued to attack after the break and spent long periods in Wolves' half, but with nothing to show for it.
Young met a half-cleared corner with a well-struck volley but De Vries, diving to his left, made a good save.
Midfielder Paul Turnbull got a sight of goal 20 yards out but his low drive flew narrowly wide, and Byron Webster lashed his shot over the bar from Young's cut-back.
Robinson just failed to get on the end of another dangerous Young cross and also blasted a shot the wrong side of the post.
But the plucky hosts were picked off on the counter-attack 13 minutes from time when Kightly raced to the byline and crossed for Ebanks-Blake to plant a simple header past Walker and into the net.
And Vokes rubbed salt in the wounds with a minute to go when he smashed Matt Doherty's cross first time into the top corner.
Whether anyone will have done enough to secure a place in the side to face Aston Villa at the weekend remains to be seen.
But McCarthy will have been pleased to see his fringe players get a decent work-out as well as book Wanderers a place in the third round of a competition they could have a decent shout of doing well in this term.