Substitute Jorge Grant bagged a brace as Gary Caldwell’s men were sent to the foot of the League Two table.
The Spireites are yet to finish a league game this season with their full quota of players after Scott Wiseman’s sending off on the stroke of half-time.
Caldwell named the exact same line up that lost on the opening day last weekend.
Ian Evatt returned after missing the cup game defeat to Sheffield United in midweek due to suspension.
The Spireites struggled to stamp their authority on the first half as the hosts had the majority of the chances.
There were nervy times early on as goalkeeper Joe Anyon spilled a free-kick.
But Caldwell’s men stuck to their task well, with the defenders throwing themselves around to get in the way of shots.
The visitors’ best chance came through newbie Gozie Ugwu, who forced a top stop from Adam Collin when he was bearing down on goal.
Wiseman was shown red for hauling down Terry Hawkridge as the County man was charging towards the Spireites’ goal.
Chesterfield got the ball into better areas after the restart, but still struggled to create anything clear-cut.
Grant had been on the pitch just eight minutes when he broke the deadlock at Meadow Lane.
The Nottingham Forest loanee netted his second goal in as many games by diverting Matt Tootle’s cross past Anyon.
And things almost got worse for the visitors minutes later as Anyon was forced to tip Jon Stead’s strike wide after Evatt was caught in possession.
Delial Brewster added some much needed impetus for the Spireites late on.
He came close to making an immediate impact after coming on, but could only fire wide.
The teenager then had an effort deflected at Collin, before heading straight at the host keeper.
Anyon made a good save late on, before Grant superbly doubled his tally with a curling free-kick into the bottom corner.
Notts County: Collin, Jones, Brisley, Duffy, Tootle (Walker, 83), Alessandra (Grant, 53), Hewitt, Yates, Hawkridge, Stead (Forte, 75), Ameobi.
Subs not used: Fitzsimons, Hollis, Hunt, Milsom.
Chesterfield: Anyon, Wiseman, Hird, Barry, Evatt, Donohue, Reed, Weir (Mitchell, 83), O’Grady, Ugwu (Maguire, 45), Dennis (Brewster, 73).
Subs not used: Lee, Sinnott, Wakefield, McCourt.
Referee: Andy Haines (Tyne & Wear)
Attendance: 7021 (1328