Goals from Etienne Capoue, Juan Zuniga and a late penalty from Troy Deeney overwhelmed the visitors, who had levelled with a solitary strike from Marcus Rashford.
For all their possession, United were unsettled by Watford’s harrying game and went behind on 32 minutes after Anthony Martial, still groggy from an earlier clash of heads, was robbed by Miguel Britos.
Daryl Janmaat picked up the ball and crossed for Capoue to fire his fourth goal of the season.
A half-time switch, which pushed Wayne Rooney further forward, settled United and they equalised on 62 minutes when Rashford scrambled the ball home after his header bounced back to him off a defender.
Watford keeper Heurelho Gomes denied Zlatan Ibrahimovic with a flying save but United always looked vulnerable and Zuniga scored from a cutback by Roberto Pereyra less than a minute after coming on.
Zuniga was then brought down by Marouane Fellaini inside the area late on to allow Deeney to score from the spot.