Matt Derbyshire struck in the first minute before Leon Best scored from the penalty spot after goalkeeper Cody Cropper brought down Richard Wood.
The visitors confirmed their dominance through Kirk Broadfoot's header and Richard Smallwood's neat finish.
Rotherham, 21st place in the table, moved nine points clear of MK Dons, who remain third bottom.
The atmosphere inside Stadium MK was tense before kick-off, but almost immediately the Rotherham fans were celebrating as Derbyshire opened the scoring.
Best then slammed home from the spot, and it was no surprise when Broadfoot and Smallwood put the game beyond MK Dons just after the break.
Ex-Miller Alex Revell almost pulled one back for the hosts, but Rotherham easily held on.
Despite languishing in the relegation zone in mid-February, Neil Warnock, Rotherham's third manager of the season, has turned his side's fortunes around, winning six of his 11 league games in charge.
MK Dons manager Karl Robinson:
"It's extremely difficult and very hard and the odds are stacked against us. We only have ourselves to blame.
"You get that tag of losing football matches and it's so hard to shift. You have to find it from somewhere to cope with the demands of this level.
"We were the better team in between the two boxes by far, (but) we are not as good as other teams in the boxes, it's as simple as that.
"I don't think it's fair to boo me individually, I don't agree with that. Collectively we have to take responsibility. "
Rotherham manager Neil Warnock:
"It was an important game but I thought it was a comprehensive victory.
"We started well with the goal and we couldn't have got off to a better start. We missed a few chances in the second half, but we can't get too greedy.
"It just goes to show what you can do with a good group who want to listen.
"I think they are amazing themselves with the ability they have and what they can do with the ball. It's a great time and we are enjoying ourselves."

The coin, said to date from the dawn of English Christianity, was unearthed in East Grafton by a metal detectorist.
Richard Bishop, from auctioneers Spink and Sons, said the final sale price was a "magnificent achievement" for such a "small but perfectly formed gold thrymsa".
Wiltshire Museum bought the coin after a fundraising campaign.
It features a head motif with a Christian cross and is believed to have been struck in modern-day France.
Experts believe it was in circulation just after the burial of King Raedwald at Sutton Hoo around AD 625.
Only five examples of this type of coin have ever been found.
Wiltshire Museum director David Dawson, said they were "delighted" to have bought the "important coin", which he said will help experts understand the importance of the Vale of Pewsey and the Kingdom of Wessex in the Saxon period.
The museum had donations from all over the world, including grants from Arts Council England, Victoria and Albert Purchase Grant Fund and the Art Fund.
Stephen Deuchar, director of the Art Fund, said: "Very few coins of such quality exist...  It's a wonderful addition to the museum's collection."
Rotherham took a huge step towards retaining their Championship status by thrashing relegation rivals MK Dons.
[NEXT_CONCEPT]
An "excessively rare" Saxon gold coin that was discovered near a Wiltshire village has been sold for £21,600.