Peter Leven bagged two goals as MK Dons recovered from a goal down to inflict Carlisle's fifth straight League loss.
Former Middlesbrough striker Danny Graham headed in for the visitors after just three minutes, before Leven drove home to equalise before half-time.
Leven then whipped in a fine cross for Miguel Angel Llera to head in at the back post and give the hosts the lead.
Jude Stirling was brought down by Danny Livesey and Leven scored the penalty to score his fifth goal of the season.
It was a fifth straight league defeat for John Ward's faltering Cumbrians, who came so close to getting promoted in May.
Milton Keynes Dons: Gueret, Cummings, Llera, O'Hanlon, Lewington, Wright, Navarro, Leven, Chadwick (Regan 84), Baldock, Gallen (Stirling 65).
Subs Not Used: Abbey, Johnson, Sturm.
Booked: Llera.
Goals: Leven 38, Llera 62, Leven 90 pen.
Carlisle: Williams, Raven, Livesey, Keogh, Horwood, Kavanagh, Joyce (Myrie-Williams 72), Taylor (Madine 73), Bridge-Wilkinson, Hackney, Graham.
Subs Not Used: Howarth, Grant Smith, Gowling.
Goals: Graham 4.
Att: 11,194
Ref: Phil Crossley (Kent).
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