Banks headed the hosts ahead in the 30th minute, before Gnanduillet added a second as the first half entered injury-time.
Chairboys were much improved after the break and Billy Knott was brilliantly denied by keeper Tommy Lee before Gary Doherty headed wide whilst unmarked, but the Blues couldn’t find a way through.
Gareth Ainsworth named an unchanged side with the only two alterations coming on the bench as Charlie Horlock (cup-tied) and Charles Dunne (international duty) returned.
Wanderers started well and enjoyed more of the ball early on and Billy Knott had the first shot of the game in the sixth minute, but his 20-yard effort was straight at Tommy Lee.
Chesterfield responded immediately and a neat one-two finished with the ball being clipped into Gnanduillet, but the striker rushed his shot when he had time and fired tamely at Matt Ingram.
Anthony Stewart produced a fine last-ditch challenge to deny Jay O’Shea in the 10th minute after the former MK Dons man was played in by Gary Roberts.
The hosts looked to stretch the play as much as possible with full-backs Drew Talbot and Ritchie Humphreys constantly overlapping, but Chairboys were coping well with Gary Doherty and Stewart dominating the penalty area.
Both defences were on top, but a piece of magic from Knott almost gave the Blues a chance to take the lead. The Sunderland loanee controlled a high ball instantly, before clipping over the defence for Craig, but his pass was just over-hit and ran through to Lee.
Despite chances being few and far between, Wanderers were almost gifted the lead in the 28th minute. Humphreys’ attempted backpass went straight to McClure and the striker turned well before seeing his shot deflected behind by Ian Evatt.
The Spireites took full advantage of their reprieve and took the lead two minutes later. O’Shea made space for himself down the right before sending an inch-perfect cross into the area for Banks to emphatically head home from eight yards.
Stewart rose above his marker to head Scowen’s corner wide at the far post and Lewis then drove over the bar from the edge of the area as Ainsworth’s men responded well to falling behind.
However, Chesterfield were to double their lead as the game entered injury-time. Roberts delivered a pin-point outswinging corner from the left and Gnanduillet jumped higher than everyone to power home a header.
Wanderers were quick out of the traps in the second half and Lee came to the home side’s rescue three minutes after the restart. Knott played a clever one-two with McClure and received the ball back in the area before striking left-footed, but Lee made himself big and made a fine stop.
Blues were much improved in the early stages and Cowan-Hall was then just unable to turn home Craig’s low cross after he had linked up with strike partner McClure.
O’Shea was lucky to escape picking up a second caution in the space of five minutes when he cynically brought down Cowan-Hall, but referee Andy Woolmer let the midfielder off with just a warning.
Ainsworth introduced former Chesterfield man Dean Morgan on the hour and the Spireites boss Paul Cook responded to Chairboys’ best spell of the game by bringing on Tendayi Darikwa and Callum McFadzean for O’Shea and Banks.
Morgan was heavily involved after coming on and he fired just the wrong side of Lee’s left-hand post after turning away from a defender on the edge of the area.
Doherty should have reduced the deficit in the 69th minute when he eluded his marker to meet Scowen’s right-wing corner, but the centre-back headed wide from six yards.
Chairboys continued to press and McCoy’s cross was just turned behind by Evatt for a corner with Craig lurking, before Morgan’s 20-yard strike took a deflection and Lee made a save low to his right.
Ainsworth made his second change with seven minutes remaining as Max Kretzschmar replaced Cowan-Hall, and the substitute had strong appeals for a penalty waved away as he went down in the area.
Knott was forced off with cramp in injury-time and despite Wanderers pressure they could not find a way through.
Wanderers: Ingram, McCoy, Wood, Doherty, Stewart, Cowan-Hall (Kretzschmar 83), Lewis (c), Scowen, Knott (Bloomfield 90), Craig, McClure (Morgan 59).
Subs: Horlock, Dunne, Johnson, Morias.
Chesterfield: Lee (c), Talbot, Humphreys, Evatt, Cooper, Hird, Ryan, O'Shea (Darikwa 61), Banks (McFadzean 61), Roberts, Gnanduillet (Doyle 86).
Subs: Chapman, Togwell, Devitt, Richards.
Attendance: 5,798 (146 Wycombe)