Both of the Spireites' goals came inside the opening eight minutes in front of almost 8,000 at Boundary Park.
Joe Quigley gave Chesterfield a first-minute lead after an error by goalkeeper Magnus Norman - and it was two soon after.
Quigley's effort this time was blocked by Oscar Threlkeld, but Calvin Miller set up Jeff King to sweep home and put the visitors firmly in control.
Latics may have feared the scoreline could get out of control, but they fought their way back into the game, with Mike Fondop a threat and Hallam Hope chipping just over before the Latics lost Dan Gardner to injury.
Jack Clarke missed a glorious Chesterfield chance and Brandenn Horton hit a post before half-time.
Quigley twice went close and former Latic Oliver Banks shot just wide from distance.
The pressure on Latics boss John Sheridan is beginning to crank up.
After the game he said: "You prepare all week, but it was massive downer at the start of the game and I don't think we recovered from it.
"I'm the manager, I pick the team, I've brought some players in - I'd like to say the three young lads who played were excellent.
"Three new lads, lots of endeavour, lots of desire, they're on loan but they're showing willingness to fight and fight and fight.
"I'm bringing people in who I think are good players, but we're not playing or performing the way we should."
Latics return to action away at Boreham Wood on Saturday.
