The Australian, who held clear-the-air talks with manager Tony Mowbray earlier this week after not figuring all season in the senior set-up, struck with 13 minutes remaining to give Boro their first triumph in three matches.
The Hornets made a fantastic start as Troy Deeney notched his second goal in three matches in the first minute after a horrendous defensive error from Andre Bikey.
Matej Vydra - returning in place of the suspended Fernando Forestieri - had a shot blocked and then hit the bar, but Watford failed to make their dominance count as fit-again Marvin Emnes levelled after 30 minutes with his third goal of the campaign.
Two minutes before half-time, Gianfranco Zola saw his side controversially reduced to 10 men for the second successive match as Vydra was surprisingly given his marching orders by referee Steven Rushton for an apparent stamp on Nicky Bailey.
And Boro made their numerical advantage count deep into the second half when McDonald, a 39th-minute substitute for the injured Justin Hoyte, converted from 12 yards to end Watford's two-match winning streak.
The hosts wasted little time in breaking the deadlock as Vydra, who has four goals to his name this season, intercepted a short backpass from Bikey and after his shot was parried out by Jason Steele, Deeney converted from close range.
Vydra was proving to be handful in the opening exchanges as Bikey had to block the striker's effort from 20 yards.
Daniel Pudil tested Steele from 20 yards before Vydra lashed a shot from a tight angle which clipped the crossbar as the Hornets continued to dominate.
However, Watford failed to build on their impressive start as Boro equalised thanks to the returning Emnes.
Manuel Almunia tipped George Friend's effort round the post and, from Grant Leadbitter's resulting corner, Emnes turned and found the net from six yards.
With their next attack, Josh McEachran brought the best out of former Arsenal goalkeeper Almunia, who superbly kept out the on-loan Chelsea midfielder's 25-yard shot.
The Hornets were rocked after 43 minutes as the lively Vydra was shown a red card for a clash with Bailey, which looked to have no malice in it.
The home side came out after the break fired up and Steele had to push away a 25-yard free-kick from Almen Abdi, who then delivered a ball into the box and Deeney headed over from close range.
Bikey almost headed Boro ahead, only to miss the target from six yards, while Almunia had to be at his best to deny Leadbitter from 25 yards.
Boro finally went in front after 77 minutes when McDonald struck from 12 yards and the visitors held on for the three points.