The clubs have battled for League Two titles, League One promotions and simply for local bragging rights.
There have been memorable play-off games (for Posh at least) and high drama with both teams recording victories after being reduced to nine men.
Players and managers who have gone on to better things have been involved in the matches
The teams have met 27 times in all competitions with Posh leading the head-to-head 12-10 with five draws.
Here is a selection of dramatic highlights from Posh v MK.
5.
May 2011: MK Dons 3, Posh 2. The first leg of the League One play-off semi-final was a dramatic affair. Craig Mackail-Smith shot Posh in front, but MK Dons scored three times in nine second-half minutes through Daniel Powell, Sam Baldock and Angelo Balenta. Charlie Lee was then sent off for Posh before referee Jonathan Moss gave Darren Ferguson's side a massive lift by awarding a penalty for a foul on Mark Little which took place outside the area and by sending off Stephen Gleeson, a decision that was soon rescinded. A grateful Grant McCann (pictured) slotted home the penalty to keep Posh in touch for the second leg. Photo: Midlands
6.
May 2011: Posh 2, MK Dons 0. One of the great London Road nights as a Grant McCann free kick, a scrambled Craig Mackail-Smith goal and a miracle tackle by James Wesolowski clinched a 4-3 aggregate victory for Posh in the League One play-off semi-final. McCann is pictured celebrating his goal. Photo: Midlands
7.
May 2011: Posh players celebrate their 2-0 League One play-off semi-final second leg win over MK. They would go on to beat Huddersfield 3-0 in the final at Old Trafford to seal an immediate return to Championship football. Photo: Midlands
8.
May 2011. The night Posh beat MK Dons 2-0 in the League One play-off semi-finals unfolded in front of one of the all-time great London Road atmospheres. The fans stayed behind to celebrate with their heroes. Photo: Midlands