Leeds were reduced to nine men early in the second half as Rodolph Austin was taken off on a stretcher after Neil Warnock had already made all three substitutions.
The hosts edged a slow start to the match and came close to taking the lead after David Norris's effort from deep inside the penalty hit the post.
Despite their strong start, it was Watford who took the lead through Matej Vydra after 28 minutes when he fired the ball into the top corner of the net from the edge of the penalty area.
Jason Pearce was then shown a straight red for Leeds after his bad challenge on goalscorer Vydra just before the break.
However, Watford doubled their lead in the 61st minute with Almen Abdi driving his effort into the bottom corner for his fifth goal of the season.
Abdi was then stretchered off six minutes later before the Horns added a third when Mark Yeates found the top corner from a free kick.
However, Leeds found a quick response from the penalty spot as Michael Tonge blasted home the spot kick.
Despite the goal, the hosts' comeback lasted just three minutes as Vydra added his second goal of the game to give Watford a 4-1 lead.
Watford move up to 12th while Leeds slip to 17th in the Championship table.