On-the-whistle report: Rotherham United 0 Luton Town 1
The Millers had been the better side before the break but were under the cosh for much of the second-half and fell to James Collins' 70th-minute goal.
It was a concerning night for manager Paul Warne who would have expected to take something from the game yet saw his men turn in one of their worst displays of the season.
Defeat left his side in 19th spot, two points above the drop zone.
Rotherham suffered an early blow when left-back Joe Mattock limped out of proceedings yet were still the first team to threaten the opposition goal.
Florian Jozefzoon's inside pass was met first time by Jamie Lindsay in the 14th minute and the midfielder's curling 20-yarder was header for the top corner until Simon Sluga pulled off a flying save.
Lindsay went close again seven minutes later as he turned Wes Harding's cross goalwards but Sluga was again there to make the stop.
The visitors - who arrived in South Yorkshire in 14th spot, with two wins in their last eight league outings - were offering little in attack at this stage, although Michael Ihiekwe had to be alert to cut out the danger as Luke Berry and Harry Cornick combined to pressure the Millers' net.
The recalled Michael Smith had a sight of goal for the home team on 36 minutes after Jozefzoon's cross but his weak shot was easily gathered by Sluga.
Smith rose highest at a Dan Barlaser free-kick only for his header to lack power and give Sluga another simple save.
As half-time approached, Luton came to life as George Moncur forced Jamal Blackman into an excellent stop with a fierce drive and Matty Pearson fired just wide on the run.
Warne had made two changes to the side that had lost narrowly at the weekend at Stoke City.
Midfielder Shaun MacDonald missed out with a knee injury and was replaced by Ben Wiles while Smith was preferred up front to Freddie Ladapo.
Striker Kyle Vassell was in the matchday squad for the first time since the 1-1 draw with Huddersfield Town a month ago.
Wiles went to left-back to deputise for Mattock after 11 minutes, with Matt Crooks entering the fray from the bench.
Smith's header over the bar from Harding's cross was the Rotherham's only effort in the opening stages of the second half and it was Luton who came closest to breaking the deadlock.
A Moncur cut-back presented Collins with a gaping goal but he couldn't sort out his feet quickly enough and then only Ihiekwe's goalline clearance prevented Cornick from scoring.
On the hour mark, Rotherham were doing most of the defending and Luke Berry saw his shot deflected wide.
Collins made amends for his miss, getting in front of the Millers defence to volley home Berry's whipped delivery.
The Millers should have been further behind soon after as Moncur raced clear only to send a tame shot straight into the arms of Blackman.
Luton were looking likely to score again and Berry rattled the post with a 75th-minute shot.
Rotherham finally rallied and substitute George Hirst headed wide in the 88th minute but for the second match in succession the Millers never really looked like equalising after falling behind.
Goals: Collins 70 (Luton).
Rotherham (4-2-3-1): Jamal Blackman; Wes Harding, Michael Ihiekwe, Angus MacDonald, Joe Mattock (Matt Crooks 11); Jamie Lindsay, Dan Barlaser; Florian Jozefzoon (Freddie Ladapo 80), Ben Wiles, Mickel Miller; Michael Smith (George Hirst 59). Subs not used: Viktor Johansson, Richard Wood, Kieran Sadlier, Kyle Vassell.
Luton (4-2-3-1): Simon Sluga; Matty Pearson, Glen Rea, Sonny Bradley, Martin Cranie; Joe Morrell (Pelly-Ruddock Mpanzu H-T), Ryan Tunnicliffe; Harry Cornick (Kazenga LuaLua 64), Luke Berry, George Moncur (Tom Lockyer 89); James Collins. Subs not used: James Shea, Elliot Lee, James Bree, Sam Nombe.
Referee: Andy Madley (West Yorkshire).