Boro's impressive start to the campaign had hit a snag when they suffered successive losses to Cardiff and Bristol City, but they got back to winning ways in front of nearly 22,000 at the Riverside this evening.
With Marvin Emnes and Ishmael Miller both on the bench, McDonald repaid manager Tony Mowbray's faith in starting him by stabbing home the opener.
Lukas Jutkiewicz and McDonald causeed the visitors' back four problems all match, but it was Emmanuel Ledesma who got the second goal with a dipping free-kick just after the hour mark.
McDonald then fired in his second of the evening, Jutkiewicz once again grabbing the assist, to extend Huddersfield's winless streak to three games.
Huddersfield started the better side. After a couple of speculative efforts went wide, Jack Hunt's mazy run culminated in a vicious left-foot strike which just whistled over the top of the crossbar.
However on 28 minutes Middlesbrough took the initiative as McDonald turned in Jutkiewicz's centre for the opener. Justin Hoyte burst into the box from his right-back berth and rolled the ball to Jutkiewicz, who in turn fired across goal where McDonald produced one of his predatory finishes.
Middlesbrough keeper Jason Steele also had to be alert to ensure Scott Arfield's dipping effort did not drop under his crossbar.
Manager Simon Grayson waited less than 10 minutes after the interval to make alterations for the visitors, introducing Adam Hammill and Chris Atkinson.
The hosts did not have to long into the second-half to double their advantage as Ledesma curled in a magical 25-yard free-kick.
The Argentinian earned the set piece himself, when he cajoled Paul Dixon into tripping him, and his curling effort dipped so low that Smithies could only push it into the roof of his net.
Jutkiewicz forced Smithies into a good save before he once more assumed his role as the provider for McDonald five minutes from time. The visitors wanted play stopped with Hunt down on the ground injured but Boro continued unabated and Jutkiewicz's cushioned header down was drilled home by McDonald to wrap up the points.