The Red Devils ran out of the Dutchman’s 29-month reign on Monday, which saw the club’s popular former striker step down from his role as assistant manager pending the appointment of a permanent head coach.
United are in talks to sign highly-rated Sporting Lisbon boss Ruben Amorim and the club appear to be safe if talks drag on, judging by Wednesday’s win against Leicester.
Van Nistelrooy – who returned to the club in the summer as one of Ten Hag’s assistants – celebrated as excitedly as those in the stands at Old Trafford when Casemiro opened the scoring with a stunner 15 minutes into his first game as interim starter.
Alejandro Garnacho struck again before Bilal El Hanous pulled one back for a much-changed Leicester, only for United to hit back after a deflected Bruno Fernandes free-kick and Casemiro’s second of the night.
Conor Coady reduced the lead in first-half stoppage time but Fernandes coolly slotted home his second goal on a night when fans’ favorite Van Nistelrooy’s name often filled the air.
United have won just one of their eight games in all competitions since beating Barnsley 7-0 in the previous round of the Carabao Cup and looked hungry after what Van Nistelrooy called a “feverish” build-up.
The caretaker boss made four changes against Leicester, whose manager Steve Cooper made nine substitutions and saw his side fall behind until a fantastic 15th-minute opener.
Fernandez intelligently got over Garnacho’s pass, giving Casemiro space to touch down and unleash a superb strike from almost 30 yards that crashed off the underside of the bar.
Van Nistelrooy raised his hands in celebration, looking as stunned as any fan by the quality of the goal.
United’s interim boss applauded another in the 28th minute.
Showing the quality and cutting edge missing in Sunday’s costly defeat at West Ham, Diogo Dalot was met by a through ball on the wing and flicked a low pass to the far post for Garnacho to head home.
Leicester’s raucous away game was muted but they found their voice again in the 33rd minute.
Altai Bayindir cleared a cross and, despite setting himself up for a try, was unable to stop El Hanous’s shot which went wide of the far post outside the Stretford End.
But hope of a comeback was short-lived, thanks in part to the Leicester scorer’s clumsy foul on Garnacho just outside the box.
Fernandes stepped up to a free-kick that took a huge deflection off James Justin, wrong-footed Danny Ward and flew into the net.
United’s third strike came in the 36th minute and the fourth followed just three minutes later.
Casemiro rose to meet Marcus Rashford’s cross with a header that bounced off both posts before reacting quickest to pounce on the loose ball.
The hat-trick-chasing midfielder narrowly missed heading in a free-kick unaware he was offside before the Foxes reduced the deficit when Dalot inadvertently headed a stoppage-time free-kick at Coady.
Leicester came back for the second half with renewed purpose, but United eventually wore them down.
Ward denied Joshua Zirkzee and couldn’t do much when Fernandez latched on to Caleb Okoli’s back pass, which rounded the keeper and then finished in the 59th minute.
Van Nistelrooy cheered when substitute Amad Diallo acrobatically curled a shot over the top with his foot and Boubakari Soumare saw a shot deflected wide of the post by Bayndir at the other end.
No further goals followed, despite United’s best efforts to add gloss to the win, which should give them a boost heading into Sunday’s home Premier League clash with Chelsea.