But Harry Redknapp's outfit were left hanging on in a hectic finish as ten man Rotherham scrapped for the equaliser.
Portsmouth oozed class from the start and swept ahead after only 14 minutes with an opener from Vincent Pericard.
The Pompey wide man darted into the area and slotted home a close range finish to punish Rotherham's sloppy defending when Matthew Taylor whipped in a danger cross from the left.
Nine minutes later Svetoslav Todorov stretched Pompey's lead with a crisp finish after another cross from Taylor had the home side in trouble.
It sparked Rotherham into action and Martin McIntosh produced his side's first effort of note but his long range shot was over the top, quickly followed by a 20 yarder from Darren Garner.
Rotherham pulled one back after 33 minutes when striker Darren Byfield claimed his first goal at Millmoor and his eighth of the season.
Byfield squeezed in his close range header as Shaka Hislop flapped at a cross from Chris Swailes.
But the first half ended in controversy when referee Graham Laws handed Portsmouth a dubious penalty after Todorov went down in the area under a challenge from Swailes.
Before ex-England midfielder Paul Merson added Pompey's third from the spot the referee red-carded Swailes and booked Mike Pollitt and Darren Garner for dissent.
But Rotherham pulled one back after 72 minutes when Alan Lee was upended in the area by Gianluca Festa before tucking away the spot kick himself,f three minutes after arriving from the bench.
And in the dying seconds Rob Scott headed wide after a Paul Warne free kick and only a splendid save from Hislop steered a Paul Hurst 25 yard shot onto the bar and out.