Boro lost ground on the leading pack in PL2 after going down 4-1 at home to Manchester United on Monday.
Two doubles for the visitors proved decisive at the Riverside as the Old Trafford youngsters emerged victorious to close the gap on league leaders West Ham United.
Boro again took the opportunity to hand minutes to a number of the youngsters who are forming part of the first team squad this season, although there was an early scare when summer signing Marcus Browne pulled up while running and was withdrawn after just eight minutes.
Boro had started the better of the two sides and after Connor Malley had a shot deflected wide, following a corner, visiting goalkeeper Matej Kovar pulled off a terrific save after a Hayden Hackney effort took a wicked deflection.
But it was the visitors who took the lead when Ben Liddle was adjudged to have committed a foul on the edge of the box and Arnau Puigmal stepped up to curl the free-kick with superb precision beyond the reach of Sol Brynn.
Less than three minutes later, Teden Mengi sent Stephen Walker tumbling to the ground inside the area, but Kovar proved equal to Liddle’s penalty, saving low to his left.
Boro pressed for an equaliser and a Marc Bola shot-cum-cross was cut out by Kovar before Malley fired into the side-netting after a couple of forays forward.
Man United were looking stronger, though, and the quick-footed Largie Ramazani shot straight at Sol Brynn before Puigmal scored his second of the evening after a Tahith Chong pull back.
Brynn was also called upon immediately after the break when he denied Ethan Laird who had cut in from the right flank.
The visitors possess the meanest defence in the league, but when Hayden Coulson did manage to get in behind them, his cross was inches away from the advancing Sam Folarin.
Walker went close for Boro with 15 minutes remaining when his glancing header beat Kovar but appeared to clip the post before falling to safety.
Boro were back in the game moments later, though, when substitute Djed Spence embarked on a forward run and fellow sub Rumarn Burrell was on hand to convert.
Brynn was called upon almost immediately to deny the visitors a third goal when he pulled off a fine save, but the keeper had no answer to the quality of Chong after a quick break when he pulled off a quality finish from a tight angle to make it 3-1 with nine minutes remaining.
And there was still time for Chong to score another with a belting strike after Boro failed to clear the ball.
Boro: Brynn, Dodds, Wood, Dale, Bola, Malley, Hackney, Liddle (Burrell 65), Coulson, Browne (Folarin 8, Spence 76), Walker. Subs, Reading, Hemming.
Man United: Kovar, Laird, Devine, Mengi, Bernard, Puigmal (Wellens 76), Mellor, Traore (Mejeri 76), Ramazanı (Elanga 57), Levitt, Chong. Subs: Woolston, Helm.