The Dons were well beaten by Macclesfield in a game where they fell behind after three minutes and never recovered.
Terry Brown made two changes from the starting line up against Hereford, bringing in Lee Minshull and Christian Jolley in place of Ricky Wellard and Charles Ademeno respectively. He also changed the formation to 4-3-3, with Luke Moore reverting to the wide left role he filled many times last season.
Before the new formation could settle down, Wimbledon found themselves a goal down after failing to deal with a long throw which was flicked on, leaving Brisley to prod the ball home from close range.
The immediate response was encouraging as Jolley got in a near post flicked header to a Jack Midson cross only to see it pushed away by the goalkeeper but, in any event, the linesman's flag was already raised. That was probably the last time the Dons threatened until the closing stages as Macclesfield took control.
The Silkmen play a fast direct style of football, getting the ball forward quickly into the channels and the spaces behind the back four, in other words perfect for counter-attacking. With the Dons needing to chase a goal, this suited them down to the ground.
The second goal came more simply than that, however, when the speedy Emile Sinclair pushed the ball past Brett Johnson and got to the bye line where he delivered a cross which Tony Diagne headed past the helpless Seb Brown.
Worse very nearly followed as Johnson might have been sent off for a foul, having already been booked, and Jolley was lucky to avoid injury following a knee high foul on him as he made inroads down the right.
Half time was reached with no more goals, leaving the 400-odd travelling fans to hope that an inspired team talk from Terry Brown might turn the tide. But any hopes were dashed when only three minutes into the second half Sinclair's speed took him past Stuart and he slid the ball home from a narrow angle, leaving Seb Brown punching the ground in frustration.
The fourth goal came late in the game when Stuart was caught in possession by Mendy, who finished clinically. There could have been more, as a deflected shot had spun over Brown's head and hit the crossbar only minutes earlier.
It was a dispiriting day for the travelling fans who were left to remonstrate with the referee for some eccentric decisions but, in truth, they made no difference to the score.
Macclesfield seemed to revel in playing against a 4-3-3 formation and, having taken the lead, they were able to play the ball around confidently. Wimbledon were never able to deal with the pace of the opposition forwards and, with confidence dented, passes started to be misplaced. All in all, the game was a lesson that even against teams who were pre-season favourites to struggle, there are no easy games in League 2.