Born in Longsight, a long stone's throw from Old Trafford, England Under-21 international Danny Welbeck calmly ensured Wolves were not able to profit from the dismissal of Fabio after just half an hour.
Welbeck finished in fine style after running on to Michael Owen's precise return pass, ensuring the holders' progress to the last 16 was smooth after a largely one-sided contest in which the loss of a player had barely any impact.
As expected, Ferguson changed his entire starting line-up from Sunday's dramatic derby draw with City.
Yet there were still opportunities for Michael Carrick and Nani, who both missed out at the weekend, plus Owen and Tomasz Kuszczak who, in their own individual way, had something to prove.
Owen has now shown his goalscoring instinct remains. Yet, as a 90-minute player he remains a bit of an unknown.
In fairness to the veteran forward, the presence of Federico Macheda and Welbeck alongside him meant he had to do more tracking back than he would normally expect and it was only after United's numbers were reduced that he really came into his own.
Kuszczak must have sensed a Premier League start at Stoke would follow an eye-catching display given Ben Foster's pitiful experience against the Blues, when he was directly responsible for one goal and hardly covered himself in glory with the last.
The Pole benefited from Fabio's departure too, producing a fine fingertip save to deny former United midfielder David Jones with the resultant free-kick.
All in all then, with the contest turning into a keenly-fought affair instead of the sterile stalemate that had gone before, the sending-off was no bad thing, except for poor Fabio, who cut a dejected figure as he made his way off the field.
In truth, the Brazilian could have no complaints.
Put in trouble by Jonny Evans' failure to win an aerial duel with the robust Stefan Maierhofer and Wes Brown over-running the loose ball which momentarily escaped his vision, Fabio looked like getting back to challenge Kightly.
Unluckily, he slipped just at the wrong moment, so in sticking out a despairing arm to prevent Kightly charging clear into the box, he brought the Wolves man down for what was ruled a professional foul.
Owen had United's best chance before the interval but could only turn a header straight at Marcus Hahnemann, who experienced his own Foster moment just before the break when his attempted clearance was charged down by Welbeck.
Fortunately for the veteran American, it bounced to safety.
A surging Welbeck run created an opportunity Darron Gibson should have done more with, and only Nani's poor cross prevented him setting up Carrick after Gary Neville had sent the Portugal wide-man racing forward.
The goal, when it eventually came, just emphasised the gulf in class.
Wolves thought they had the situation under control when Gibson rolled a sideways pass to Carrick 30 yards out.
But within an instant, the England midfielder had created space for Welbeck, whose first time pass was returned in equally promising manner by Owen, who succeeded in providing his young team-mate with an opportunity to run onto the ball, clear of the Wolves defence.
The finish was first-time too. Straight into the bottom corner, as befits a player currently making the graduation from England Under-19 to Under-21 duty and surely destined for even higher honours one day.
Welbeck departed to a standing ovation from United's lowest crowd for four years - which still exceeded 50,000 - for another teenager, Norwegian Joshua King, of whom very big things are expected.
With a bit more composure and a little bit of luck, King might have marked his debut with a goal too, although ultimately one proved to be enough.