The Red Devils, who won the last of their 12 FA Cups in 2016, suffered a 2-0 defeat to Manchester City in the semi-finals of the EFL Cup on Wednesday, while Watford will enter the contest off the back of a 2-1 defeat to Swansea City in the Championship on January 2.
United's recent form has been excellent, winning eight of their last 10 in the Premier League to rise into second position in the table, level on points with leaders Liverpool.
The Red Devils will have the chance to move to the summit on Tuesday, ahead of the trip to Liverpool on January 17, as they play their game in hand against Burnley at Turf Moor.
Ole Gunnar Solskjaer's side saw their EFL Cup challenge come to an end on Wednesday night, though, as they suffered a 2-0 defeat to bitter rivals Man City in the semi-finals of the competition.
The league will take priority for United this season, but Solskjaer wants to deliver a trophy as soon as possible, and the FA Cup might arguably be the team's best chance of silverware this term.
The 20-time English champions, as mentioned, have won this competition on 12 occasions, the last of which was in 2016; they reached the semi-finals of last season's tournament, but David de Gea had a match to forget against Chelsea as the Blues recorded a 3-1 victory to advance.
Watford, meanwhile, will enter the match off the back of a 2-1 defeat at Swansea, which left the Hornets down in sixth position in the Championship table.
A record of 10 wins, seven draws and five defeats from 22 matches has brought the Hertfordshire club 37 points, which has left them 10 points off the top of the division, a spot which is currently occupied by Norwich City.
Watford suffered a 4-1 defeat to United when the two teams last met in the FA Cup back in 2007, with Wayne Rooney inspiring the English giants to the final.
The Hornets have actually lost six of their last seven matches with the Red Devils in all competitions, but they recorded a 2-0 win when the two teams met at Vicarage Road in December 2019.
Manchester United FA Cup form: DWWWWL
Manchester United form (all competitions): WWDWWL
Watford FA Cup form: WWWLDL
Watford form (all competitions): WWDLWL
Facundo Pellistri had potentially been in line to make his debut for the club, but the youngster has tested positive for coronavirus and will therefore not be involved.
The hosts are expected to make a number of changes from the side that started against Man City as they will face Burnley in the Premier League on Tuesday ahead of a trip to Anfield.
Anthony Martial could be on the bench against Burnley on Tuesday with Cavani serving the final game of his three-match suspension here, meaning that the Frenchman might start this contest.
Head coach Xisco will also make alterations to his first-choice XI, with Daniel Bachmann and William Troost-Ekong among those in line for starts, but midfielder James Garner is ineligible to face his parent club.
Manchester United possible starting lineup:
Henderson; Tuanzebe, Bailly, Maguire, Telles; Matic, Van de Beek; James, Mata, Greenwood; Martial
Watford possible starting lineup:
Bachmann; Navarro, Troost-Ekong, Wilmot, Masina; Hughes, Chalobah, Cleverley, Sarr; Gray, Deeney
We say: Manchester United 3-1 Watford
Watford are certainly capable of making it a very uncomfortable 90 minutes for United, who will have one eye on their next league game at Burnley. The Red Devils have had their problems at Old Trafford this term, but we expect them to advance to the fourth round of the FA Cup courtesy of a 3-1 success.