James Vaughan's goal was his second of the season for Wigan
Wigan's James Vaughan scored the only goal as Rotherham suffered their third away defeat of the new season.
Vaughan forced the ball home after goalkeeper Marek Rodak failed to hold Callum McManaman's initial effort.
Rodak had earlier kept the Millers on level terms with a superb double stop to deny Callum Connolly and McManaman.
Ryan Williams went close to an equaliser with a low effort from Kyle Vassell's cross, but Christian Walton made a fine fingertip save.
Rotherham boss Paul Warne's plans were disrupted early when they lost defender Sean Raggett to injury, with Clark Robertson coming on his place.
After Joe Mattock blocked a goalbound effort by Connolly, Josh Windass was only inches away from an opener for Wigan when his free-kick flew just wide of the top corner.
Ryan Manning tested Walton with a 25-yard attempt just before the break and the keeper had to save again from Mattock's effort following a free-kick early in the second half.
Substitute Vaughan, though, had the decisive say as he toe-poked the ball over the line and Wigan held out fairly comfortably for all three points.
Wigan assistant manager Leam Richardson said:
"It was certainly a hard-fought victory.
"Rotherham made us work tirelessly for it, as we knew they would do.
"But our lads dug in and we really earned the win."
Rotherham boss Paul Warne said:
"I'm obviously biased, but I'm also honest and I thought we were the better side in the second half.
"Against an excellent Wigan side, who played Stoke off the park last week, I'm proud of the effort and how we went toe to toe with them.
"But at the same time I'm very disappointed to come away with nothing."
