Carlton Morris had given the Hatters a first-half lead, but the Latics fought back to take the points with two goals in the last ten minutes as Tom Lockyer deflected a Callum Lang shot past his own keeper and Thelo Aasgaard curled in an 88th minute winner.
Nathan Jones made one change to the side that won at Cardiff in midweek, as Gabe Osho came in to start after scoring his first goal for the club in South Wales, replacing Reece Burke who missed out through injury.
Sonny Bradley returned to the bench, along with Harry Cornick who featured in the matchday squad for the first time since the Carabao Cup defeat to Newport County.
Fred Onyedinma could also be called upon once again after making a positive impact at Cardiff as the Hatters continue their search for a first home win of the season.
Town had the first opening when Morris flicked Jordan Clark's pass into Adebayo's path on the edge of the box, but Wigan keeper Ben Amos was quickly off his line to deflect the striker's attempted chip behind for a third-minute corner.
The visitors soon had a chance of their own, James McClean dragging a shot wide of the near post amid a couple of early corners, but it was the Hatters who were making the early running without creating any clear-cut chances.
James Bree saw a 17th-minute shot fly well wide, and there was no real attacking action of note until ten minutes before half-time, when Freeman drew a flying save out of Amos with a 25-yarder that was destined for the top corner.
Lockyer volleyed the resulting set-piece at goal, only for Wigan captain Max Power to hack clear off the line, then Morris saw a shot on the turn deflected behind as the Hatters turned the screw.
The breakthrough finally came on 39 minutes when a short corner routine found its way to Bree, who stood a beautiful cross up for Morris to attack. The top scorer did just that, heading his third goal of the season into the same top corner as he did against Sheffield United eight days earlier.
The chance for a second came two minutes later when Allan Campbell's determined run down the right win took three Wigan defenders out, and his driven cross flew across the face of goal, diverted away only by Ryan Nyambe's outstretched right leg.
Wigan had the first chance of the second half, ten minutes in, when Will Keane headed over from a corner, before Jones made his first change, replacing Adebayo with Cauley Woodrow in the 55th minute.
Clark tried to make inroads down the left, sending in a low cross that just eluded Woodrow, then midfield partner Campbell raced into the box, latching onto a lay-off from Morris, but saw his shot blocked behind by Jack Whatmough racing across.
Wigan struggled to clear the corner, and from Woodrow's lay-off, Osho checked back onto his left-foot to arc a shot towards the far top corner, but just off target.
Callum Lang headed McClean's cross wide with just over 20 minutes remaining, as Jones prepared to make his next two changes - Cornick making his return in place of Freeman, and Cameron Jerome on for Morris.
Town survived a big penalty shout when the ball hit Lockyer's chest, then Jerome went down under challenge by Tilt at the other end with referee Chris Kavanagh unmoved.
Wigan's equaliser arrived with ten minutes remaining - Nyambe charging down Bell's attempted clearance up the line by the left corner flag, then crossing low for Lang who managed to get a shot off, which was heading across the face of goal until it hit Lockyer and beat Horvath.
Jones introduced Onyedinma for Clark and Luke Berry for Campbell, but it was Wigan who broke away take the lead with two minutes remaining with Lang squaring for substitute Thelo Aasgaard curling home from the edge of the area.
The Hatters had the ball in the back of the net and thought they snatched an equaliser in added time but for the linesman's flag on the far side to condemn Jones' side to a third league defeat.
GOALS:
LT - Morris 39
WA - Lockyer (OG) 80, Aasgaard 88
ATT: 9.885 (1,035 away)
