Headers from Dean Lewington and Darren Potter, plus Stephen Gleeson's cool finish condemned Rovers to their third straight defeat on the road.
Lewington put the Dons ahead in the 10th minute when he nodded in the rebound after Dean Bowditch's exquisite 25-yard curler had come back off the crossbar.
Mamady Sidibe missed a golden opportunity to equalise for Tranmere when he completely mis-timed his header from six yards and Gleeson made him pay by doubling the Dons' lead two minutes before the break.
Gleeson raced clean through on to Shaun Williams' arrowed 60-yard pass and coolly slotted the ball first-time past Tranmere keeper Owain Fon Williams for his sixth goal of the season.
Potter made it 3-0 five minutes after the break when he headed the rebound into an empty net after Williams' 22-yard free-kick had struck the crossbar.
Tranmere pressed for a consolation goal in the closing stages, but Zoumana Bakayogo wasted their best chance when he blazed Jean-Louis Akpa-Akpro's cutback high over the crossbar.