Murray Wallace's early header ensured that Millwall will be in the quarter-finals of the FA Cup for the second time in three years and ended AFC Wimbledon's record-breaking run in the competition.
The south-west Londoners had never before reached the fifth round and hit the post inside the first few minutes through Joe Pigott before the Scot converted with the only notable moment of an uneventful first half.
The game ebbed and flowed far more after the break, with Neil Harris' men spurning a number of opportunities, with 20-year-old Michael Folivi managing the Dons' only shot on target.
Republic of Ireland internationals Aiden O'Brien, Shaun Williams and Alex Pearce all started for the Lions.
Both teams reached this stage thanks to notable scalps in the last round. The Dons belied their lowly league status to humble West Ham United 4-2, while Millwall twice had to come from behind to defeat Everton 3-2 at The Den.
Despite being rooted to the bottom of League One, Wally Downes' men started this tie with plenty of zest after overturning the Hammers and they really should have taken the lead just a few minutes in when Shane McLoughlin's purposeful run down the right was followed by a sumptuous cross which was glanced off the post by top scorer Joe Pigott.
The underdogs were made to pay moments later, when Ryan Leonard drove down the wing and his delightful delivery was met by a thumping header by Murray Wallace which had AFC Wimbledon goalkeeper Aaron Ramsdale snatching at thin air.
To their credit, the home side did not allow their heads to drop, but their lack of a cutting edge indicated why they are languishing at the foot of the third tier.
Going into the break, the only effort on target had been the goal and Downes seized the initiative by bringing on Andy Barcham for Tyler Garratt.
The former Portsmouth winger was already offering more of an outlet, but with around 55 minutes on the clock, Millwall could have doubled their advantage when Lee Gregory's run was picked out and the Lions' top scorer held up the ball before laying off to the onrushing O'Brien, whose effort was clawed away by Ramsdale.
The game was starting to become far more open and Murray Wallace's hanging cross was headed wide by Jake Cooper at the far post, before the hosts thought Jon Moss had awarded them a penalty when Barcham was clipped when attempting to reach the loose ball. Alas, he was offside.
As AFC Wimbledon started to throw more caution to the wind, they were leaving more spaces at the back, with Ramsdale having to be alert as both Gregory and Leonard looked to put the tie to bed.
As the game reached the first minute of stoppage time, Jed Wallace burst through and was about to pull the trigger before a thundering challenge by Mitchell Pinnock.