On-the-whistle report: Rotherham United 2 Preston North End 1
The Lilywhites arrived at AESSEAL New York Stadium with the division's best away record of four wins and a draw.
But it was the much-changed Millers who, after two defeats, triumphed with second-half goals from Richard Wood and Matt Crooks.
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Hide AdWood volleyed the home side ahead, Preston equalised through Ryan Ledson and substitute Matt Crooks steered in the winner late on.
Manager Paul Warne got the response he wanted after the loss against Luton Town three days earlier as his side turned in a peformance full of spirit and endeavour.
The result saw them remain 19th in the table but put more distance between them and the teams below them.
The Millers made a bright start but neither side tested the opposing goalkeeper early on.
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Hide AdJamie Lindsay tried his luck after eight minutes for the home team but the ball skewed off the outside of his boot and went well wide.
Paul Huntington headed a free-kick just wide for the visitors before Kyle Vassell wasted a good opportunity for Rotherham.
The attacker had a clear sight of goal on the left in the 16th minute but took too long to get his shot away, allowing Huntington to get in a block.
The Millers were doing most of the attacking but the services of their debutant goalkeeper, Viktor Johansson, were required on 25 minutes. His first serious action for the club saw him beat out the attempt of Daniel Johnson who had been sprung clear by Emil Riis Jakobsen.
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Hide AdFreddie Ladapo threatened in the 35th minute when he got on the end of Dan Barlaser's long pass and worked himself a shooting opportunity only to drag his low effort wide from the edge of the area.
Three minutes later, Vassell's free-kick piledriver was pushed away by Declan Rudd for a corner.
Warne had promised to freshen up his side after a flat second-half showing against Luton Town in midweek and he was good to his word.
Summer signing Johansson came in for his first start because of Jamal Blackman's ankle injury and the boss made five other changes.
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Hide AdMatt Olosunde was in at right-back, with Wes Harding switching to the left, and Wood returned at centre-half.
Striker Ladapo was recalled and there were call-ups for winger Kieran Sadlier and Vassell, neither of whom had seen first-team action in recent weeks.
New keeper Josh Vickers, whose signing was announced the day before the game, was on the bench.
Six minutes after the break, Rotherham should have gone ahead when brilliant skill down the left by Ben Wiles set up Ladapo who steered the cross wide with the net at his mercy.
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Hide AdBut they didn't have to wait much longer for the breakthrough, as skipper Wood controlled Michael Ihiekwe's head-back from a free-kick only seconds later and volleyed home.
Johansson added to an impressive debut showing on 69 minutes, coming out bravely and quickly to deny Tom Barkhuizen in a one-on-one confrontation.
However, he was powerless ten minutes from time when Ledson was lurking at the edge of the area to fire a cleared corner low and hard into the net.
Rotherham were back in front five minutes later when Florian Jozefzoon drove up the pitch and gave the ball to Crooks to apply the finish at the kop end.
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Hide AdPreston hit the post in time added on through Jayden Stockley and Barkhuizen dragged a shot wide, but the Millers could have added to their lead when Jozefzoon was clean through and denied a goal by Rudd.
Goals: Wood 53, Crooks 85 (Rotherham); Ledson 80 (Preston).
Rotherham (4-4-1-1): Viktor Johansson; Matt Olosunde (Angus MacDonald 89), Michael Ihiekwe, Richard Wood, Wes Harding; Kieran Sadlier (Florian Jozefzoon 23), Jamie Lindsay, Dan Barlaser, Ben Wiles; Kyle Vassell (Matt Crooks 67); Freddie Ladapo. Sub not used: Josh Vickers, Mickel Miller, George Hirst, Michael Smith.
Preston (4-1-4-1): Declan Rudd; Darnell Fisher (Paul Gallagher 75), Paul Huntington, Jordan Storey, Joe Rafferty; Ryan Ledson; Scott Sinclair (Tom Barkhuizen 59), Alan Browne, Daniel Johnson, Brad Potts; Emil Riis Jakobsen (Jayden Stockley 59). Subs not used: Connor Ripley, Josh Earl, Josh Harrop, Sean Maguire.
Referee: Andy Davies (Hampshire).