A late double from the Spireites sealed the victory to send the Spireites to the top of the League Two table.
Two goals from substitutes, Armand Gnanduillet and Tendayi Darikwa sealed the emphatic victory after David Connolly was earlier sent off for an off the ball incident.
Chesterfield named the same side that started the game against Southend last weekend, which meant Ian Evatt had to wait another week for his second debut in a Spireites shirt.
After Paul Cook applauded the fans in usual fashion before an away game, and to the huge noise from both supporters, the game kicked off.
Patrick Agyemang and David Connelly started brightly for the home side, winning two corners within the opening five minutes, but both were dealt with by the Spireite defence.
It was the Spireites who had the ball in the back of the net soon after, however the linesman’s flag denied an early goal. Gary Roberts set Marc Richards through one-on-one and the striker finished with ease, but the whistle had already been blown.
Although Portsmouth had more of the ball, it was Chesterfield that came closest to opening the scoring. Drew Talbot carried the ball into the box and fed Jay O’Shea, but his effort was superbly saved by the goalkeeper.
Chesterfield started to silence the home crowd by keeping the ball. Richards had an effort from the edge of the area, but it didn't trouble John Sullivan in the Pompey goal.
Ten minutes before the break, the referee turned down a strong penalty appeal from the home side as Liam Cooper looked to bring down Connolly.
Minutes later, the striker saw red for an off-the-ball incident. Connolly appeared to knock Sam Hird to the ground and the linesman indicated to the referee that it was a red card.
Ritchie Humphreys could have put the Spireites ahead immediately after. The midfielder was put through by Richards, but he took just too long and the Portsmouth defender intercepted the chance.
The red card seemed to lift the home supporters, but it was Chesterfield that dominated. O’Shea picked up the ball on the angle of the box and unleashed an effort that just evaded the cross bar.
The half time whistle was greeted with a chorus of boos from the home support as it ended an action packed first half, without goals.
The game restarted and it was Portsmouth that had an early free kick which caused the biggest cheer of the afternoon. Ricky Holmes took it but it didn’t beat the ball and the danger was cleared.
Five minutes into the half the Spireites put together a great flowing move but O’Shea couldn’t apply the finish from 25 yards. The attacker couldn’t keep his shot down as the ball rocketed into the crowd.
O’Shea received the first booking of the afternoon for the Spireites as he unfairly challenged Danny East.
The referee again seemed to deny Pompey a penalty, not giving the decision much to the dismay of the home supporters.
A substitution for both sides on the hour mark as Richards was replaced by Eoin Doyle and Agyemang left the game in replace of Ryan Bird.
After ten minutes of Spireites dominance without really creating many chances, Chesterfield brought on Gnanduillet in place of Nathan Smith and reverted to a four-four-two formation.
The target man made an instant impact, knocking the ball down for Doyle to run on to, but the goalkeeper claimed the ball.
With ten minutes remaining, Portsmouth nearly snatched a goal. Sonny Bradley charged out of defence and took it past three onrushing Spireites players, his shot was initially saved by Lee. The ball spilled to Andy Barcham but the winger’s effort went the wrong side of post.
The game became end-to-end as Doyle was causing problems in the Pompey defence. Darikwa was introduced in place of O’Shea with five minutes remaining.
Chesterfield eventually took the lead with only minutes remaining. The two substitutions, Doyle and Gnanduillet, combined superbly; the Irishman’s cross found the head of the Frenchman and he nodded home his second goal in consecutive weeks.
Bird had an effort that wasn’t troubling Lee, as the fourth official indicated a minimum of four additional minutes.
The Spireites sealed the victory in added on time as Darikwa extended the Spireites lead. Again, the substitutes combined as Gnanduillet fed Darikwa and the winger finished from an acute angle to send Chesterfield to the top of the Sky Bet League Two table.
Portsmouth: Sullivan; Moutaouakil, East (Craddock 88'), Devera, Bradley, Barcham, Connolly (c), Holmes (Wallace 74'), Ertl, Ferry, Agyemang (Bird 64').
Subs not used: Smith, N'Gala, Padovani, Butler.
Chesterfield: Lee; Smith (Gnanduillet 71'), Hird, Cooper, Talbot (c); Ryan, Morsy, O'Shea (Darikwa 84'), Roberts, Humphreys; Richards (Doyle 64').
Subs not used: Chapman, Togwell, Devitt, Edwards.
Goals: Portsmouth 0 - 2 Chesterfield (Gnanduillet 87', Darikwa 90+2')
Attendance: 15,999 (957 Chesterfield)