After falling behind to an unfortunate Alex Lacey own goal midway through the first half, the Glovers produced four second half goals to make it eight games unbeaten at home in all competitions.
Kevin Dawson and Francois Zoko both found the net from the penalty spot, before Alex Lacey scored his first Town goal with a sublime finish after Samir Carruthers was sent off for the Dons.
With the game already beyond doubt Ben Whitfield rounded off the scoring, to continue Town’s impressive run of form.
Darren Way made four changes to the side that extended their Sky Bet League Two unbeaten run to eight matches at the weekend with the 5-0 demolition of Crawley Town.
Fresh from moving into the play-offs, Town gave starts to Jonny Maddison, Matt Butcher, Tahvon Campbell and Zoko in the Trophy, with Artur Krysiak, Alex Lawless, Otis Khan and Tom Eaves all shifting to the bench.
Despite facing Sky Bet League One opposition, the Glovers enjoyed the majority of possession in the opening exchanges, looking to carry on where they left off at Huish Park three days ago.
However, goal scoring opportunities were proving hard to come by with only a long-range Kevin Dawson strike to mention in the opening 20 minutes, which flew over Lee Nicholls’ goal.
At the other end Maddison was largely a spectator, before the 22-year-old had to fetch the ball from his own net with 24 minutes on the clock in unfortunate circumstances.
A long ball over the top from the Dons saw Maddison come off his line to collect, but unaware of his keeper’s advancement, Lacey could only direct his header into the now vacant net to gift Robbie Neilson’s side the lead.
Now trailing, the Glovers searched for an immediate way back into the match and enjoyed a succession of corners after smart work down the right from Zoko and Campbell, as Town switched to a diamond 4-4-2 formation.
As the game ticked towards to half-time it was the visitors who came closest to a second goal of the evening.
Wideman Daniel Powell blazed an effort wide from the angle, before Kabongo Tschimanga had a close-range effort saved by Maddison, with the rebound trickling out for a goal-kick after ricocheting off the Dons academy graduate.
That was as good as it got in a relatively tame opening 45 minutes, as Way’s side trailed at the break in a half that seemed unlikely to create a goal until the Glovers defensive mishap.
But, having not last at home in seven matches, Yeovil levelled the scores just three minutes after the restart.
Campbell had his heels clipped in the box by Paul Downing, allowing Dawson to pick out the corner from 12 yards after referee Lee Swabey pointed to the spot.
The Glovers impressive start to the half continued after equalising as Town entrenched themselves in the Dons half, before winning a second spot kick on the hour mark.
With the ball pinging around the box Mr. Swabey spotted a handball, with Zoko stepping forward this time to send Nicholls the wrong way and complete the comeback.
The Buckinghamshire outfit were struggling to contain a rampant Yeovil side and after picking up a yellow card for a cynical foul on Ben Whitfield on 57 minutes, Samir Carruthers received his marching orders 10 minutes later for a mistimed tackle on the same man.
Yeovil soon made the most of their numerical advantage and added a third with a little under 20 minutes remaining.
Dawson rampaged down the right before swinging in a cross which found its way to Alex Lacey who had ventured forward from defence, with the centre back producing a superb first time finish to pick out the top corner and make amends for his earlier own goal.
Fresh from scoring five at the weekend Way’s side seemed determined to repeat the feat, adding a fourth on 79 minutes with a well worked goal.
Neat build-up saw Campbell feed Ryan Dickson out wide, with the left-back’s pinpoint first time cross being headed home by Whitfield past a hapless Nicholls to make it 9 goals in two games at Huish Park.
The Glovers continued to search for more goals in front of the home faithful but had to settle for four, as Way’s side saw off higher league opposition in emphatic style to reach the Round of 16 in the Checkatrade Trophy.
Yeovil Town: Maddison; Shephard, Lacey, Smith, Dickson; Dawson (Lawless 82’), Butcher, Whitfield; Hedges (Khan 86’), Campbell, Zoko (Eaves 80’).
Bookings: Campbell 35’, Smith 45’
Subs not used: Krysiak, Ezewele, Lawless, Copp, Sowunmi.
MK Dons: Nicholls; G.C. Williams, Hendry, Downing, Tilney; Carruthers, G.B. Williams; Powell, Aneke (Agard 59’), Colclough (Reeves 59’); Tshimanga (Baldock 71’).
Bookings: Carruthers 57’, 67’ (red), Hendry 67’
Subs not used: Martin, Walsh, Furlong, Thomas-Asante.