Boro secured a first win under new manager Wilder by ending Huddersfield’s five-game unbeaten run at the John Smith’s Stadium.
Watmore struck twice early in the first half to give the visitors a healthy advantage.
And Wilder’s men were seldom under threat until a late consolation goal as the hosts were condemned to their second consecutive defeat.
Wilder took one point from six after replacing Neil Warnock as Boro boss but an important victory in West Yorkshire lifted his side up to mid-table in the Championship.
Both sides lacked rhythm in an edgy opening as Terriers midfielder Scott High threatened to unlock the Boro defence with a curling through ball towards Danny Ward.
But just moments later, Wilder’s men took the lead after cutting the hosts apart on the break.
Watmore found himself in ample space after Isaiah Jones’ cross and clinically finished past Lee Nicholls in the 16th minute.
Carlos Corberan’s Huddersfield had kept clean sheets in their last four home games but the Spaniard’s side were uncharacteristically unorganised early on.
And the visitors were rampant as Watmore was superbly set up by Huddersfield academy graduate Matt Crooks to delightfully lob Nicholls on the half volley for his third league goal of the season.
Huddersfield could not live with Watmore’s movement and the forward turned defender Tom Lees before striking straight at Nicholls as he sensed a quick-fire hat-trick.
Wilder’s impressive side regained total control before the pause as the hosts failed to muster a single shot on target.
Corberan’s men left the field to a chorus of boos after a dismal first period littered with mistakes in possession and defensive lapses.
Boro started the second half as they ended the first, cutting through the hosts almost at will.
Midfielder Marcus Tavernier was played through on goal after some tidy interplay but his effort was foiled by the onrushing Nicholls, who reacted well to close the angle.
The hosts looked to breathe life into an insipid performance in search of a response but the compact three-man Boro defence remained resolute and the visitors were far more dangerous.
Buoyant Watmore turned provider for Slovenia international Andraz Sprorar, who fired just wide with his left foot.
Corberan made attacking changes in a bid to rescue the game as Josh Koroma and Fraizer Campbell replaced Harry Toffolo and Duane Holmes.
Boro had a huge penalty claim waved away after Tavernier’s shot struck Lees in the box.
Lewis O’Brien’s pull back was deflected in for an own goal by goalkeeper Luke Daniels in the final seconds, but Middlesbrough held on for a deserved victory.