Czech Republic striker Vydra, signed on loan by Gianfranco Zola from Italian side Udinese in the summer, fired home in time added on at the end of the first half and struck his second in the 83rd minute to ensure Watford consolidated their play-off place.
Scott McDonald headed home a consolation for Boro in the third minute of stoppage time.
Vydra's opener was the visitors' first effort on goal and Boro, chasing their fifth straight home league win, were left wondering how they had failed to score after creating a hatful of first-half chances and several more after the break.
Zola's side, unbeaten in their last six away npower Championship games, have now won seven on the road this season.
Defenders Seb Hines and George Friend, midfielders Josh McEachran and Faris Haroun, plus strikers Scott McDonald, Emmanuel Ledesma and Lukas Jutkiewicz all returned to Middlesbrough's starting line-up.
Spanish goalkeeper Manuel Almunia was back following a hamstring injury to skipper Watford, while Cristian Battocchio made his second start of the season and fellow midfielder Almen Abdi also returned.
Boro, not surprisingly, took time to adjust, but made all the running in the first half.
Ledesma's 30-yard effort in the second minute warmed Almunia's hands and Jutkiewicz's shot from inside the penalty area was blocked by Watford defender Joel Ekstrand. Friend then blasted the subsequent corner over the bar.
Australian forward McDonald was next to test Almunia with a vicious 25-yard shot and Jutkiewicz dragged a left-footed effort wide from the edge of the area in the 16th minute.
Hines then blazed his shot from six yards off target from Grant Leadbitter's corner as Boro did everything bar score in the opening half an hour.
Watford saw enough of the ball, but by the time Almunia had turned away Ledesma's angled shot in the 42nd minute, the visitors had failed to muster a single effort on goal.
But in time added on at the end of the first half Watford struck against the run of play with their first shot of the game.
Vydra pounced on a loose ball in the area and drilled a left-footed shot beyond Boro goalkeeper Jason Steele into the bottom corner.
Boro were still reeling after the restart and Vydra forced Steele into his first save when blocking the striker's 20-yard shot.
Abdi, back from a pelvic injury, and Ledesma traded long-range strikes that flew wide before Boro's on-loan Chelsea teenager McEachran was forced off injured in the 57th minute and replaced by Adam Reach.
Reach (twice), Ledesma and Faroun all tried their luck from outside the area, the latter's superbly held by Almunia before Boro boss Mowbray sent on Ishmael Miller for Jutkiewicz in the 69th minute.
Substitute midfielder Merouane Zemmama was then sent on for Ledesma as Mowbray looked to salvage a point, but Watford went close to extending their lead when Vydra's close-range effort forced a fine reflex save from Steele.
But Steele was helpless when Vydra steered home his second in the 83rd minute, taking Abdi's cross from the left in his stride to bury another finish into the bottom corner.
McDonald headed home Reach's cross in the 93rd minute, but it was a mere consolation.
- Sports & Recreation
- Manuel Almunia