Gareth Ainsworth's men have been in superb form so far this campaign, but were undone at St James Park as goals from David Wheeler and Scott Bennett earned Exeter the points after Peter Murphy had initially given Wycombe an early lead.
Burton Albion are now level with Wycombe at the top of England's fourth tier following their enthralling 4-3 victory at Carlisle United.
Damien McCrory gave Burton a fifth-minute lead that was quickly cancelled out by Kyle Dempsey before three goals in the space of 20 minutes put the visitors in command.
Brad Potts' strike in the fifth minute of stoppage time offered Carlisle hope at the end of a first half that saw Burton lose defender George Taft to injury in the third minute.
Derek Asamoah then cut the deficit to one in the 65th minute, but Burton held on, although Stuart Beavon was sent off in second-half injury time.
Striker Mark Cullen scored a hat-trick as Luton Town extended their unbeaten league run to eight matches to move up to third with a 3-1 success against Dagenham and Redbridge.
Luton leapfrog Bury following their 5-0 hammering at the hands of Shrewsbury Town, Ivorian forward Jean-Louis Akpa Akpro putting the Lancashire club to the sword with a treble.
Micky Adams began his reign as Tranmere Rovers boss with a 0-0 draw with Mansfield Town, while Russ Wilcox was denied a first win as York City manager as Jack Redshaw's 94th-minute equaliser salvaged a 1-1 draw for Morecambe.
Defender Joe Devera scored in the 79th minute to give Portsmouth a thrilling 3-2 triumph against Stevenage and Danny Hylton netted twice as Oxford United overcame Northampton Town 3-1.
A sparse crowd of 947 saw Accrington Stanley beat Hartlepool United by the same scoreline, while a Josh Coulson own goal gifted Cheltenham Town a 2-1 away win versus Cambridge United.
Elsewhere, midfielder Myles Weston was made to pay for missing a penalty as Southend United lost 1-0 at Newport County and AFC Wimbledon drew 0-0 with Plymouth Argyle.
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