The Dons delivered another stunning stadiummk performance as they cruised to a Club record victory over Colchester United.
Afobe then scored his 18th goal of the campaign to wrap up his first career hat-trick just before the hour mark.
Ben Reeves made it 5-0 from the penalty spot midway through the second half, and Lee Hodson put the icing on the cake in injury-time with a superb curling effort.
Kyle McFadzean, Daniel Powell and Afobe replaced Tom Flanagan, Dean Bowditch and Will Grigg in the starting XI for the clash with the U’s.
The Dons created a chance as early as the first minute with Antony Kay heading Reeves’ corner not too far over Sam Walker’s crossbar.
Despite the men from MK1 starting brightly, they almost went behind in bizarre circumstances three minutes later when McFadzean inadvertently turned Elliott Hewitt’s teasing cross on to the post with David Martin stranded.
The centre-back came very close to scoring at the right end on eight minutes but Walker did brilliantly to get down and push away his downward header from a Reeves corner.
Alli did find the back of the net on 11 minutes, and it was some goal too. After bursting away from his marker, the 18-year-old arrowed a stunning 25-yard effort into the bottom left-hand corner – his eight goal of the season.
Fantastic covering from Hodson thwarted Freddie Sears as the visitors momentarily threatened on the counter-attack just past the quarter-hour mark, which the Dons dominated.
The hosts’ best outlet was Powell down the left-hand side and he continued to cause major problems with his pace and power, but Karl Robinson’s side couldn’t find the second goal, for the time being anyway.
However, it did arrive in the 37th minute when Carl Baker perfectly picked out Afobe, who let the ball run across his body before coolly slotting past Walker from 15 yards.
The pair were again involved on the stroke of half-time to extend the Dons’ lead, the latter heading home from close range after the lively Baker had initially seen a fierce effort well saved by Walker.
McFadzean came within inches of making it 4-0 in the opening minutes of the second half as he poked Baker’s cross on to the post from eight yards.
Reeves then curled a 20-yard effort just past the left-hand post as the Dons kept their foot on the gas while, at the other end, Sears tested Martin with a long-range effort.
Afobe completed his first career hat-trick in style on 57 minutes, bursting past the U’s defence before firing low past Walker into the bottom right-hand corner to make it 4-0.
It was 5-0 10 minutes later when Reeves made no mistake from the penalty spot after Afobe was hauled down by Birmingham City loanee Will Packwood, who was subsequently shown a red card.
The Dons continued to push forward in search of more goals and 18-goal man Afobe saw a 20-yard saved while the visitors were also having to deal with a number of balls into their box.
Flanagan forced a goal-line clearance from fellow substitute Danny Green’s corner with just over 10 minutes remaining prior to Darren Potter firing a speculative effort wide of the target with Walker off his line.
The men from MK1 saved the best goal till last as left-back Hodson cut in and curled a magnificent effort into the top right-hand corner from 20 yards in injury-time.
MK Dons: Martin; Spence, Kay, McFadzean (Flanagan 68), Hodson; Potter (c), Alli (Green 63); Baker (Grigg 73), Reeves, Powell; Afobe.
Subs: McLoughlin, Baldock, Bowditch.
Goals: Alli (11), Afobe (37, 45 & 57), Reeves (67), Hodson (90+1).
Attendance: 7,646 (309 away fans).