A brilliant 3-1 Spireites win saw Northampton's amazing unbeaten run out for 31, on a day of happy firsts at the Proact Stadium.
Paul Anderson pulled one back for the Cobblers but Kristian Dennis scored his first EFL goal on his first Chesterfield start to restore the two-goal cushion and confirm a home win to end Northampton's streak.
The Spireites started the game brightly with Dion Donohue winning his side a corner within seconds of the kick-off, but 'keeper Adam Smith was able to punch away the set piece.
After eight minutes Wilkinson opened his Chesterfield account with a fine drilled finish across the goalkeeper from inside the box after Jay O'Shea had spotted the on-loan striker on the shoulder of the defender.
Veteran Matt Taylor flashed a long-range effort wide for the visitors, before Jay O'Shea dazzled round his man on the left but saw his ball float marginally over Kristian Dennis in the centre.
The Spireites were inches from a second midway through the half when Gboly Ariyibi skipped to the byline, brought a ball back towards Dennis, a defensive deflection sending the ball in until it was spectacularly hooked off the line by a Cobblers man.
The Spireites attacks continued and after Dennis had mis-kicked an Ariyibi pull-back, Wilkinson latched onto possession and looking to make room for a shot was stopped by a fine Zander Diamond tackle in the box.
The latest push forwards from the hosts was close again, Ariyibi played into space down the right. The winger pulled a ball back towards Nolan that took a defensive toe into Dennis's path, a shot came in, but was blocked as it flew goalwards.
The hosts were having the better of things but Northampton's potency was shown seven minutes before the break when Alex Revell headed down for Harry Beautyman to volley goalwards, but Sam Hird blocked the shot.
The visitors were close again on the stroke of the interval as an inswinging corner produced a scramble in the six-yard box that the home fans were pleased to see ended by an offside flag as the Spireites retained the lead into half time.
Wilkinson took just four minutes to score a second after the break as the striker took advantage of Paul McGinn's diverting overlap to shoot from 23 yards into the back of the net via a slight deflection.
The home side were looking comfortable with their two-goal lead, but it was reduced to just one on 63 minutes when Anderson beat Donohue to a ball at the back post and managed to poke a shot into the far side of the goal.
The goal gave the visitors belief and substitute Marc Richards brought a renewed attacking edge against his former side.
However, the fourth goal was the Spireites' as Donohue sped forwards in tandem with O'Shea on 70 minutes and drove a shot that Dennis was able to divert home from near the penalty spot for his first ever EFL goal.
Chesterfield: Wilkinson 8' 49', Dennis 71'
Northampton Town: Anderson 63'
Attendance: 5,910 (736 away fans)