Rotherham secured their ninth away win of the season thanks to an Alex Revell double.
Revell scored in each half as Rotherham took control with some excellent football.
It was only in the final minutes that they had to hold on after Andy Robinson pulled one back in the 90th minute but Rovers boss Ronnie Moore could have no grumbles at losing to his former club who were the better side throughout.
A brilliant save denied James Tavernier’s 25-yarder as Rotherham began to dominate in the first half and Lee Frecklington went close from the edge of the area. He was denied by Owain Fon Williams, but Rotherham were not to be denied themselves and went ahead on 39 minutes.
Kieran Agard linked up with Kari Arnason and his low cross saw Revell drive home on the turn from 10 yards.
Right on half-time Rotherham looked to be denied a clear penalty when Agard was brought down by Matt Pennington.
Rotherham should have extended their lead when Wes Thomas, in his first start, moved onto a header from Revell and a goal looked certain but he struck his shot wide.
Thomas was involved when Rotherham extended their lead on 64 minutes. He got clear only for Fon Williams to block the shot, the ball rebounded towards Revell, who finished emphatically.
Tranmere ensured a nervy stoppage time for Rotherham when Robinson netted after his first header came back off the bar.
Tranmere Rovers: Fon Williams Pennington Taylor, Arthurworrey, Horwood Kirby (Robinson 59, , Wallace Jennings (Koumas 74), Kennedy (Stockton 78); Cassidy, Lowe. Unused substitutes: Holmes, Goodison, Power, Mooney.
Rotherham United: Collin; Bradley, Davis Arnason Tavernier Agard Frecklington (Vuckic 88), Milsom (Smallwood 71), Pringle Revell Thomas (O’Connor 81). Unused substitutes: Skarz, Turgot, Hitchcock, Thompson.
Referee: D Drysdale (Lincs).