It was a positive first half performance from the Hornets but they still found themselves behind at the break. Marcus Rashford gave the hosts the lead with a tap-in with around 10 minutes left to play before half-time.
It was an uneventful second half as the Hornets desperately tried to get themselves back into the match, but they could not prevent United from ending their league campaign on a high.
Rashford tap-in puts United ahead
Despite the fact that United had very little left to play for in this match following their 0-0 draw against West Ham United in midweek which secured them second place, José Mourinho still named a strong starting line-up.
There was talk that Mourinho might give a couple of United's youngsters a chance to shine on the big stage but this was not the case.
Ahead of the FA Cup final next weekend against Chelsea, Alexis Sánchez was named in the starting line-up as well as 36-year-old midfielder Michael Carrick, in what was the last game of his playing career.
As for Watford, Javi Gracia opted to make three changes to his starting line-up. This saw Heurelho Gomes, Gerard Deulofeu and Richarlison come in for Orestis Karnezis, Étienne Capoue and Troy Deeney.
United started the game poorly, making a number of sloppy errors which the Hornets perhaps could have done better with.
The likes of Richarlison, Deulofeu and Andre Gray were looking particularly dangerous in the opening exchanges which gave the travelling supporters hope that they could achieve a positive result on their final outing of the season.
Rashford was given another chance to make an impression from the start, albeit mainly due to Romelu Lukaku's absence. The 20-year-old had a difficult start to the game but started to become more involved with around half an hour played.
It looked as though the striker may have been played through on goal by Juan Mata but his touch let him down and the chance had soon gone, much to the frustration of the home crowd.
However, he was able to get himself on the scoresheet just minutes later. On his 464th appearance for United, Carrick played a delightful ball over the top to find Mata, who unselfishly squared the ball to Rashford for a simple tap-in to make it 1-0 to the hosts.
Falling behind did not dishearten the Hornets, who had another two chances to level before half-time. Firstly, Sergio Romero kept out a point-blank header from Richarlison as he tipped the ball around the post. Deulofeu then had a chance from the resulting corner but could only fire his shot directly at the United keeper.
United hold out in uneventful second half
Similarly to in the first half, it was Watford who made the brighter start to proceedings. However, despite getting themselves into promising areas on a number of occasions, they were struggling to create any clear chances in front of goal.
It took United a while to get going, but they did create a number of opportunities following the restart.
With just over 20 minutes left to play, Sánchez almost picked out Mata at the back post with a lobbed cross but the Spaniard could not get on the end of it.
Despite the fact their side still found themselves a goal behind, the away fans did have a reason to be cheerful in the latter stages as Nathaniel Chalobah came on to replace Gray, and end his eight month spell on the sidelines through injury.
There was still time for Watford to put some pressure on the hosts in the final few minutes, but it was not enough to prevent United from winning their 25th game of the season and finishing in second place on 81 points.