The League One side got off to a flying start with Armand Traore putting through his own net after just four minutes and Ryan Lowe doubled the lead five minutes before the break.
Things got worse for QPR with Ryan Harley netting a third for MK Dons on 50 minutes and Darren Potter got in on the act six minutes later to pile the misery on Harry Redknapp's side.
Jay Bothroyd and Fabio da Silva netted two late goals to reduce the arrears, but it could not spoil MK Dons' day.
The hosts started the better in west London and found the back of the net after just 52 seconds, with Bothroyd setting up DJ Campbell to slot home.
That strike was ruled out for offside and QPR's bright start was soon brought to an abrupt end when Shaun Williams' fourth-minute corner to the near post was put into his own goal by Traore under pressure from Dean Lewington.
After that MK Dons were penned back and were reduced to hopeful efforts, with Dean Bowditch striking wide on a rare voyage forward, but QPR were made to pay for such generosity in front of goal five minutes from half-time.
A long ball from Anthony Kay caught QPR, namely Anton Ferdinand, napping and Lowe slotted past Rob Green to double the Dons' advantage.
Things got worse for QPR five minutes into the second half as MK Dons struck again as Lowe broke the offside trap and pulled back from the by-line for substitute Harley, who could not miss from close range.
Dave Martin palmed over an Alejandro Faurlin header, before the Dons amazingly made it 4-0 in the 56th minute when Potter curled home past Green.
In a bid to change things, Bobby Zamora came on for his first appearance since November 10. QPR captain Park Ji-sung was the man that made way and was jeered off the pitch by the home fans.
Bothroyd nodded home in the 83rd minute after Zamora's tee-up, and Fabio scored in stoppage time from a Bothroyd touch, but it proved just a consolation on a terrible day in the Hoops' recent history.