Both managers made changes going into the clash at Selhurst Park, with Roy Hodgson calling upon the services of Joel Ward and James McArthur, to replace Nathaniel Clyne and Jairo Riedewald.
Whilst Chris Wilder made three changes to the side that lost 1-0 to Burnley last time out; as Jayden Bogle was handed his first Premier League start, with John Fleck and Oliver Norwood also returning to starting line-up.
It would be the home side who would make the brighter start to the game, with the Eagles finding themselves 1-0 up after just three minutes.
Andros Townsend released Wilfried Zaha down the left-hand side, who cut the ball back to Christian Benteke. His deflected flick-on set free Jeffrey Schlupp, who made no mistake in slotting home past the helpless Aaron Ramsdale.
Schlupp's effort marked Palace's quickest Premier League goal since 2017, and more importantly, put the South London side 1-0 ahead - a position they had not lost from in their last 29 games.
The Blades were limited in their chances in the early exchanges, as Palace held firm against a side that has not won in the league this season.
Schlupp went down on the 35th minute mark, holding his right knee and having to go off, making way for summer signing, Eberechi Eze.
Wilders' side built momentum as the half went on, having their best and only effort on goal in the first half just after 40 minutes. Ethan Ampadu put through Jayden Bogle, however, he could only blast his effort straight at Palace keeper, Vicente Guaita.
Following the injury to Schlupp, five minutes of injury time was added on to the first half. It would be Palace who would capitalise on this.
Eze found himself in space in his own half and drove at The Blades' defence. He skipped past three helpless defenders and exquisitely slotted past Ramsdale to put the Eagles two up on the stroke of half time.
The second half saw 45 minutes of limited chances as Palace looked to defend their lead.
Christian Benteke went off just one minute into the second half with a dead leg. Jordan Ayew was the man to replace the Belgian.
Chris Wilder handed a debut to 16-year-old, Antwoine Hackford, late on, becoming Sheffield United's youngest ever Premier League player and their second youngest overall after Louis Reed.
Andros Townsend found himself in good space in the 85th minute, after a cross from Zaha. Townsend managed to get a shot off from the edge of the box, but John Fleck was in the way to divert the ball out for a corner.
It would be Hackford that would have the best chance of the second half for the visitors. Chris Basham played the ball back from the byline, but the youngster's effort was blocked by the Eagles' resolute defence.
Palace held on and secured an impressive 2-0 victory and their second clean sheet of the season.
Eze's bright future
Eberechi Eze is vital for Palace. His ability to carry the ball from defence to attack so quickly really helps a Palace side that historically have not always been the best in front of goal. His presence also takes the weighty pressure off Zaha's shoulders, when he is not firing on all cylinders. Today being a good example of that.
The Blades poor showing once again
Wilders' side looked lacklustre yet again today. Not only were they absent in front of goal, they failed to get themselves into the positions needed to have any chance of scoring. The ship may have already sailed for Premier League survival.
Man of the Match - Ebere Eze
The Man of the Match award could have gone to a few of Palace's players; but Eze's solo effort on the brink of half time made him the deserved recipient. Tyrick Mitchell and the centre-back pairing of James Tomkins and Cheikhou Kouyate all deserve a mention, holding strong and limiting the visitors to very few clear-cut opportunities.
Both sides are away from home in FA Cup matches as the Premier League takes a week off.
Crystal Palace travel to Wolverhampton Wanderers on Friday evening in an all-Premier League affair. Sheffield United take on Bristol Rovers on Saturday, a game that they will be desperate to win as they remain firmly planted at the bottom of the league.