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Preston's interest in the Championship play-offs was ended by a Sheffield United side who ended their home campaign with a win.
The Blades secured automatic promotion with victory over West Bromwich Albion at Bramall Lane in midweek, but the visitors could have retained hopes of a top-six finish with a victory.
They briefly threatened to do just that in the second half when on-loan Manchester City striker Liam Delap scored his first goal for the club to equalise Anel Ahmedhodzic's headed opener.
The Blades roused themselves with goals from John Fleck, Iliman Ndiaye and Oli McBurnie to end their home campaign with a flourish and ensure the Lancashire club will stay in the Championship next season.
Ryan Lowe's side could have no complaints, as they were second best all afternoon and have now lost three consecutive away games for the first time in a year.
Bramall Lane is not a happy hunting ground for Preston, with just two wins in their past 21 visits, but after the Blades celebrated clinching the return of their Premier League status days earlier, their fans travelled in the hopes of catching Paul Heckingbottom's side at a weak moment.
Preston manager Lowe appeared to lower expectations on the day before the game, claiming that his squad was punching above their weight as they had the "20th" budget in the division.
The expected onslaught from the visitors failed to materialise, with Josh Onomah's tame shot into the hands of goalkeeper Wes Foderingham, their only reasonable first-half goal attempt.
The Blades were slow to get going but Freddie Woodman had to be sharp to deny James McAtee one-on-one before they moved ahead on 36 minutes.
Defender Ahmedhodzic was allowed a free leap by Patrick Bauer and Alvaro Fernandez and headed Tommy Doyle's corner in off the post to give United the lead.
Lowe responded by switching to a back four at half-time, and sending on striker Delap, who has been quiet since joining the club in January.
He got on the end of Brad Potts' driven cross to briefly revive Preston hopes, but as they pushed for a winner the home side simply picked them off on the break.
Substitute Fleck drove at the defence and got the benefit of a lucky deflection to restore the Blades' lead and thee minutes later the outstanding Ndiaye got on the end of a sprint and cross by Daniel Jebbison to put the result beyond doubt.
Another substitute McBurnie applied the finishing touch with a volleyed finish when Chris Basham's cross reached him.
Sheffield United manager Paul Heckingbottom told BBC Radio Sheffield:
"The team was excellent - the approach and mentality. Any time you play on a Wednesday night and then again on a Saturday, your margin for error and for recuperation is reduced.
"We also celebrated fairly well on Wednesday into Thursday, so it was all about our mentality and approach and I couldn't be any prouder of the staff and players. The performance was excellent and the scoreline reflected that.
"Picking the team was about having six players on the pitch who could last 90 minutes, and that's not us taking the game lightly.
"We were all together celebrating and then we were all together preparing for this. It has been a remarkable season - we have two games left and want to win them, get over 90 points."
Preston manager Ryan Lowe told BBC Radio Lancashire:
"My emotions are high at the moment so I'll be careful what I say. I'm disappointed obviously as I wanted to take it to the last day of the season and give ourselves a chance.
"I've just said to the group in there that if they don't want to follow suit, then move on because I'm not hanging around to take a bang-average team through the division.
"I need a team of men, of good-quality players, a team of players who are going to do what I ask them to do, which they've done for large parts of the season.
"But when you fold the way we folded there, it's disappointing."
