Czech Republic striker Matej 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.
Scott McDonald headed home a consolation for Boro in the third minute of stoppage time but it wasn't enough to prevent Tony Mowbray's side from losing for only the second time in their last 10 outings at the Riverside.
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, and as a result, Boro took time to adjust, despite making all the running.
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.
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.
But Watford scored with their first shot on target. Vydra pounced on a loose ball in first-half injury time before firing a drilled left-footed shot into the bottom corner.
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.
But Watford doubled their advantage 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.