Manager Micky Adams recalled striker Darius Henderson and midfielder Lee Williamson to his starting XI against their former club, but was left to regret his decision as the former Hornets pairing both saw red in the space of six minutes.
Striker Danny Graham had already put the home side ahead after some dreadful defending gifted him his 23rd goal of the season and second-half goals from Martin Taylor and Ross Jenkins made sure.
Watford announced this week they are on the verge of a takeover by a group led by entrepreneur Laurence Bassini, and keeping hold of Graham is likely to be top of the new chairman's wishlist.
The visitors, however, will struggle to keep any of their top players if they are relegated to npower League One. Defeat left the Blades six points from safety with nine games remaining.
A scrappy opening spell saw neither side take a grasp of the game before the hosts took a 10th-minute lead.
Don Cowie crossed the ball in from the right and defender Neill Collins made a dreadful attempt of his clearance which saw him volley the ball goalward.
Steve Simonsen made a wonderful reflex save to keep the ball out, but Graham was left with a simple chance and scored a header from three yards.
Henderson - making his first start for United since last April after recovering from a serious hamstring injury - had been given a warm reception from the home crowd, but soon found himself in the referee's book for a late challenge on John Eustace.
Strike partner Sam Vokes flashed a header wide from Henderson's cross as the visitors mounted a spirited response, but Henderson then saw red in the 28th minute.
Again the striker was late as he closed down a clearance, and after catching Lee Hodson referee Dean Whitestone was left with no option but to show a second yellow card.
There was a lengthy delay as Hodson was treated and the young full-back was taken off on a stretcher.
Play eventually resumed and Williamson was then dismissed for a 34th-minute challenge on Lloyd Doyley.
Doyley was first to the ball and headed clear as Williamson followed through to clatter him with a hefty challenge which was punished by a straight red from Whitestone.
Graham shot wide as the first half came to a close and teed up Eustace for a long-range drive at the start of the second period as the Blades looked to hold on.
But Taylor found the second goal in the 57th minute.
Cowie's corner was headed goalward by substitute Adam Thompson, and while Simonsen again made a fine save to tip the ball onto the crossbar, Taylor was able to stab the loose ball in from close range.
Cowie thrashed an effort over the top before another substitute Jenkins grabbed a third with four minutes left.
Eustace delivered a dangerous cross from the right and Jenkins found space to power a header into the bottom corner.
Watford 3-0 Sheff Utd: Match Report - view commentary, squad, and statictics of the game as it happened.