James McClean's strike meant that it was a fourth defeat of the new campaign for Paul Warne's side, who slipped to 19th, after the goal came about through their failure to deal with a long ball midway through the first half.
That defeat was also the Millers' third loss in their last five, with a victory over rivals Sheffield Wednesday the only highlight in a poor run of form.
After welcoming the Hatters to the New York Stadium, Rotherham will then face a home tie against a Preston North End side who boast the best away record in the league and are unbeaten away from Deepdale this season.
From Luton's perspective, they can have no complaints about the loss to Brentford on the weekend as they were blown away, conceding two in the first 29 minutes.
Like Rotherham, Luton come into this fixture with three losses in their last five and will be hoping to get back to winning ways at the New York Stadium.
With 13 points from nine games, it has been a mixed start for the Hatters but given last season's relegation scare, they will be pleased to have forged a foundation from which they can propel the rest of their season.
Rotherham are the first of two away games in four days for Luton as they travel to Huddersfield Town on Friday and could have an opportunity to leapfrog the Tykes before entering the international break.
Rotherham United Championship form: DLDLWL
Luton Town Championship form: WLLWDL
Paul Warne admitted that not making adjustments to his lineup may have cost the Millers on the weekend, and so is expected to ring the changes for this one to avoid another jaded performance.
Rotherham United possible starting lineup:
Blackman; Harding, Ihiekwe, Wood, Mattock; Sadlier, Wiles, Barlaser; Jozefzoon, Ladapo, Miller
Luton Town possible starting lineup:
Sluga; Lockyer, Pearson, Bradley; Cranie, Rea, Morrell, Norrington-Davies; Mpanzu, LuaLua; Collins
We say: Rotherham United 2-0 Luton Town
Both sides have been in mixed form of late, but Rotherham will have grown in confidence after a good home win against Sheffield Wednesday and we are backing them to continue that run against the Hatters.