Juan Mata’s penalty in the first-half was followed by two late goals from substitutes Marcus Rashford and Mason Greenwood in the latter stages of the contest, which didn’t reflect the effort Town put into the 90 minutes.
Nevertheless, Luton’s impressive cup run was brought to an end as attention immediately switches to the derby match against Watford on Saturday.
Manager Nathan Jones made nine changes following Saturday’s 2-1 victory against Derby County in the Sky Bet Championship, with captain Sonny Bradley and left-back Rhys Norrington-Davies the ones to keep their place in the side.
Peter Kioso made his first competitive start for the Hatters and looked assured from the off, although it was the away side who dominated possession and had the better chances early on.
James Shea was kept busy from the beginning, he denied Mata in the opening stages and the Spaniard once more in the 14th minute, after a nice flowing move from United.
But the Hatters weren’t to let pressure from the five-time League Cup winners peg them back and created chances of their own.
First the ex-United youngster Ryan Tunnicliffe drove forward and released Danny Hylton, who’s first-time effort hit the side-netting.
Adding continued pressure as the half went on, Jordan Clark went close to marking his birthday with a goal, but his deflected effort fizzed over the bar.
However just before the half-time whistle was blown, George Moncur was penalised for a foul on Brandon Williams in the penalty box. Mata took responsibility from 12-yards and sent Shea the wrong way to give United the lead in the 44th minute.
Bradley and Tunnicliffe produced some great defending after the hour mark, first to block Odion Ighalo’s shot after the striker ran from halfway into the Town box. Then to prevent Lingard’s effort from crossing the line, as the skipper volleyed the danger clear.
Shea was busy once more as he saved well with his legs to deny Donny Van de Beek from close range before Town came agonisingly close to an equaliser.
Andrew Shinnie’s free-kick from the right was met firmly by Tom Lockyer. Dean Henderson saved his initial header and the defender’s rebound straight after was cleared off the line miraculously.
A triple substitution of Fernandes, Rashford and Greenwood changed the context of the game, with the two England internationals both getting on the scoresheet at the end of the match.
That ended Town's chance of a last-16 trip to either Preston North End or Brighton & Hove Albion as United progressed into the next round of the competition.
Town: Shea, Kioso, Bradley (C), Lockyer, Norrington-Davies; Tunnicliffe, Shinnie, Moncur (Lee 76); Clark (Cornick 76), LuaLua, Hylton.
Subs not used: Sluga, Cranie, Pearson, Mpanzu, Collins.
Yellows: Kioso, Hylton
Manchester United: Henderson, Wan-Bissaka, Bailly, Maguire (C), Williams; Matic, Fred, Van de Beek (Fernandes 79), Mata (Greenwood 79), Lingard; Ighalo (Rashford 79)
Subs not used: Grant, Dalot, James, Mengi.
Goals: Mata (44), Rashford (88), Greenwood (90+2)
Yellows: Williams
Referee: Tim Robinson
