Huddlestone was one of three midfielders to find the net for the Tigers with Mo Diame and Sam Clucas also netting as Steve Bruce's side displayed exactly why they are at the top of the Championship tree going into the international break.
The Tigers were impressive in every department as they produced a powerhouse display as they extended their unbeaten run to 12 matches.
Diame steered home the Tigers opener just before the break with Clucas diverting David Meyler's miscued shot past Dimi Konstantopoulos to add a killer second on 67 minutes.
A majestic long-range strike from Huddlestone seven minutes from time then applied the coup de grace as Hull powered to their fifth league victory on the spin and their fifth consecutive clean sheet.
Bruce made two changes to his starting line-up, with Harry Maguire, as expected, making his first league start for Hull in place of Alex Bruce, who injured his groin in the 2-0 midweek win at Brentford.
Meanwhile, Diame was also named in the starting XI, in place of Chuba Akpom, who has to settle for a place on the bench, with the Tigers likely to employ a 4-4-1-1 formation.
Boro head coach Aitor Karanka made three changes to the team who beat Rotherham United 1-0 in midweek, with their no place in the starting side for regular captain Grant Leadbitter.
Manchester City loanee Bruno Zuculini started in the middle of the park with Adam Clayton, while Diego Fabbrini was restored to the line-up in place of Carlos De Pena.
Defensive enforcer Dani Ayala, celebrating his 25th birthday, came in for Emilio Nsue, with Tomas Kalas switching to right back and Fernando Amorebieta keeping his place in the starting line-up ahead of Ben Gibson.
George Friend was handed the captain's armband for the Teessiders.
By Championship standards, the hype ahead of the game was considerable and the eagerly-awaited spectacle did not disappoint in an excellent first-half which saw Hull rewarded close to its conclusion after an imposing final twenty minutes.
After a quiet start, Hull started to force the issue, but not before they had a let-off with Boro spurning a fine chance to break the deadlock on 16 minutes.
Fabbrini, who buzzed around with intent all half, slipped in Nugent down the right and from an acute angle, he saw his low shot fly a whisker wide after the Tigers defence had been undressed.
An offside flag then denied Boro after Fabbrini almost played in Nugent with an exquisite defence-splitting pass.
The approach play from both sides was of very presentable order and the tactical battle an intriguing one with Hull fashioning out a good chance on 24 minutes.
David Meyler was fouled just outside the 18-yard box with the free-kick responsibility entrusted to the impressive Clucas, whose pinpoint effort was tipped over in the nick of time by a scampering Dimi Konstantopoulos.
Soon after Boro were caught short after being dispossessed in midfield with Diame, another enjoying an eye-catching half, finding Clucas who played in Elmohamady with Boro short of numbers down Hull's right.
The Egyptian saw the whites of Konstantopoulos's eyes but the Boro keeper got his angles right to hold onto the Hull winger's angled low strike.
Hull was starting to show the assertion and gain a stranglehold in the midfield and forced several corners, with Boro's rearguard forced into overtime.
That said, Boro possessed threat on the break with a raking pass from Stewart Downing almost catching them out, with Albert Adomah latching onto the ball down the left before cutting inside - but a key saving challenge by Moses Odubajo, who had slipped initially, saved the day.
Diame soon twisted and turned in the box before a vital Boro clearance before Elmohamady glanced a header just wide after a well flighted corner from Clucas.
The visitors defence cracked just before the break when more adept play from Hull saw the ball played out to Elmohamady on the right and with Boro's stretched, his centre was dispatched by Diame, arriving right on cue in the box to steer the ball coolly home from eight yards out.
The Tigers held sway on the restart, with Boro making a change on 51 minutes when Kike came on for Nugent.
Half-chances arrived for Hull, with Diame showing neat footwork before firing over and soon after Michael Dawson made a timely run to latch onto Clucas's free-kick, but his header was straight at Konstantopoulos.
On the back four, Boro were starting to look ragged and devoid of ideas with Hull firmly in the box seat.
It was somewhat of a surprise when Boro conjured an excellent moment out of nothing, with an exquisite crossfield pass from Downing picking out Friend, whose near-post effort was brilliantly blocked by Allan McGregor.
It was not the prelude to Boro dominance with Hull producing a game-breaking second midway through the half.
It may have had a touch of fortune to it, but Hull's reward could not be doubted.
Meyler's miscued low shot was drifting wide, but Clucas stuck out a leg to divert his off-beam effort past the stranded Konstantopoulos.
Hull proceeded to see out the rest of the game out in comfort as they head into the international break in the highest of spirits, with their mood buoyed even further by a brilliant late effort from Huddlestone - four minutes after coming on for Diame.
Odubajo, another who had an outstanding game, fired a late chance as Hull scented a fourth.
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