It took just three minutes for the Belgian striker to fire the Red Devils ahead with a great bit of individual work in a contest predominantly controlled by the hosts.
Lukaku struck the fatal blow on 55 minutes though, getting on the end of a sublime United break to fire home his second of the match and 20th of the season.
Lukaku's well-taken early goal gives United a perfect start
United would've been craving an early goal in front of the usual raucous John Smith's Stadium crowd to stamp their authority on the match and Romelu Lukaku provided that in just the third minute.
A slick one-two with Juan Mata on the half-way line got the Belgian in behind Christopher Schindler, who he easily out-tussled inside the box before cutting in on his right and firing low past Jonas Lössl at his near post from eight yards out.
Despite going behind early, Huddersfield were in control of proceedings in the opening stages and almost issued an instant response on six minutes through Tom Ince.
Luke Shaw was playing Ince onside which helped Philip Billing give him the ball in a promising position on the left side of the box, but Ince snatched at his effort and hit it across the face of goal and wide.
More VAR controversy concludes first half run by the hosts
The hosts' pressing was relentless and Florent Hadergjonaj continued to show attacking intent from right-back, testing Sergio Romero with a ferocious long-range effort on 15 minutes but the Argentinian goalkeeper got down well to hold the ball and prevent the danger.
Romero was called into action again six minutes later, having to scuttle across his goal to collect Collin Quaner's glancing header after getting on the end of Danny Williams' cross from the right.
Mata latched onto Ashley Young's through ball from the right and thought he'd somehow given United a two-goal cushion going into half-time in the 45th minute, but was harshly denied after Kevin Friend conferred with his VAR.
The Spaniard seemingly beat the offside trap the collect the ball inside the box and cooly take it round Lössl before slotting into an empty net inside the six yard box - even the linesman's flag wasn't raised.
The Red Devils and Lukaku start the second half just as they did the first
Scott McTominay very nearly sent Alexis Sánchez, in space with a clear look-in on goal, through one-on-one with Lössl at the start of the second half, only for Mathias Jørgensen's heroic intervention to cut out the danger.
Huddersfield were back on top before we knew it though and threatened again after a Tom Ince free-kick from 20 yards out deflected into the path of Rajiv van La Parra inside the box.
However, the Dutch forward swung at the ball, missing it completely in a great position and was made to pay five minutes later when Lukaku doubled his tally for the evening and United's lead.
The Terriers' high line was undone by a superb United break on 55 minutes as Sánchez fizzed into the opposition half, set Lukaku off and the big frontman used his pace and power to calmy fend off defenders and stroke past Lössl with his left.
Another FA Cup Quarter-Final awaits Manchester United
Sánchez carried on showing his playmaking class just past the hour mark, lifting a delightful ball over the defence for Lukaku to take before he tried to play Mata in on goal, but Lössl shot out quickly to claim.
Lukaku's second ended up being to deafening blow to Huddersfield's chances in the clash and although the home crowd and players remained high-spirited, no more notable action was to take place and José Mourinho's side secured their place in the quarter-final draw.
David Wagner and co. will continue their quest for Premier League survival on Saturday in what is a crunch match-up against West Bromwich Albion at the Hawthorns.
Next up for Manchester United, the return of Champions League football on Wednesday night in Sevilla.