The 24-year-old opened the scoring on 41 minutes at the New York Stadium, giving Rafa Benitez's side the advantage at the end of a half in which Rotherham applied plenty of pressure.
And, despite both sides managing to carve out goalscoring opportunities after the break, a solitary goal was all United required to extend their unbeaten run to four games in all competitions.
Benitez made two changes from the side that beat Norwich City 4-3 at St. James' Park on Wednesday night.
Winger Atsu was handed his first start since his arrival on loan from Chelsea in place of Matt Ritchie, and the United boss also brought back Vurnon Anita - who missed the last three games through suspension - with DeAndre Yedlin named among the substitutes.
On the opposite flank to Atsu was Yoan Gouffran, and he had two early sights of goal. Cutting in from the left, the Frenchman saw his first shot blocked before his second was held by goalkeeper Lee Camp.
Gouffran again went close 12 minutes in, connecting with Atsu's cross from the right and volleying goalwards, but the retreating Dael Fry cleared it off the line, with Camp beaten.
Camp's opposite number Darlow was tested for the first time shortly after, tipping Joe Newell's dipping effort over the bar as Rotherham rallied. Jon Taylor's shot took a deflection off Paul Dummett and skimmed the crossbar, with the hosts growing in confidence.
With Alan Stubbs' men enjoying a spell of dominance, Tom Adeyemi dragged one wide from distance, as the division's bottom side looked to upset the form table.
But back came the Magpies, with Dwight Gayle fizzing in a cross from the right which evaded Gouffran at the far post, and Atsu turning in the box before the Millers managed to scramble away his centre.
And four minutes before the break, United broke, with Jonjo Shelvey feeding Atsu on the right. From there, the Ghanaian international shifted inside on to his favoured left foot and curled a beauty of a shot over Camp and into the far corner to give Benitez's side the lead at the break.
Just after the restart, with Newcastle attacking the end housing the 2,500 travelling supporters, Atsu's flick gave Gouffran a chance to pull the trigger, but his powerful shot was deflected over. Minutes later, Shelvey curled in a free kick towards Gayle, who got a toe to it but couldn't direct it goalwards.
Then, Mo Diame split the defence with a terrific through ball which released Atsu, and his goalbound shot had to be turned away by Camp, who got down low to his right to keep it out. Anita burst down the right just after the hour and squared for Diame, but his shot was blocked and the resulting corner cleared.
Wideman Ritchie was introduced for Atsu after the hour, and Benitez's side continued to put pressure on Rotherham. Shelvey curled one that was bound for the bottom corner, until Camp intervened, pushing it away.
Ciaran Clark then glanced a Shelvey corner just wide, but Greg Halford's deflected shot and the subsequent corner, from which Rotherham struck the woodwork, indicated that the Millers weren't yet done.
But Newcastle weathered that storm and held on to ensure they would go into the international break on the back of a victory.