The Whites could see their two-year spell in the top flight come to a devastating end if they fail to get a result at the Brentford Community Stadium.
Just two seasons after former United boss Marcelo Bielsa was the architect of Leeds' long-awaited Premier League return, the West Yorkshire side have become embroiled in an immensely tight fight for survival.
United's failure to repeat the remarkable form which led to last season's ninth-placed finish has given them no chance to climb clear of the bottom of the table and ultimately led to the sacking of Bielsa in February.
His replacement, Jesse Marsch, has endeavoured to bestow clarity and belief on a set of players disheartened by the events of the campaign and in various states of fitness as the LS11 injury crisis has refused to let up.
Additionally the suspended Luke Ayling and Dan James will sit out the final day showdown after being shown straight red cards in the Whites' games against Arsenal and Chelsea respectively.
As United's fight to survive in the Premier League goes right down to the final day, here's what you need to know about the all-important decider:
What time is kick-off?
All ten Premier League games will kick off simultaneously on the final day of the season.
Brentford v Leeds United will kick off at 4pm on Sunday May 22.
Is it on TV? How can I follow the game?
Brentford v Leeds United will be broadcast live on Sky Sports Football and Sky Showcase, with coverage starting at 2.30pm.
The YEP will have you covered with a live blog bringing you all the build-up, in-game updates and post-match reaction and analysis live from the Brentford Community Stadium.
What happened last time the teams met?
A late goal by the returning Patrick Bamford helped United to a dramatic 2-2 draw on the reverse at Elland Road in December.
After missing nine games to an ankle injury, the Whites striker stepped off the bench to poke home from a corner in the fifth minute of injury time.
Leeds have not won away to Brentford since August 1950.
How are Brentford doing?
The Bees have enjoyed a remarkable maiden Premier League season and could claim an impressive ninth-placed finish with a win against Leeds.
On Sunday, Leeds visit a club enjoying a strong finish to the season - of their last ten games, the West London side have won seven.
Last time out, Brentford claimed an eventful 3-2 win at Goodison Park, where the Bees came from behind twice to beat an Everton side who had just nine men at the final whistle.