The Chairboys, playing at this level for the first time in their history, had lost their opening seven games but stopped the rot against the Hornets.
Ismaila Sarr put the visitor ahead shortly after half-time at Adams Park but Anthony Stewart levelled for Wycombe and it held out for a memorable result.
Reading scored inside 10 seconds as it continued its best start to a season for 35 years with a 4-2 win at Blackburn.
The Royals are a surprise package after unknown boss Veljko Paunovic's appointment midway through pre-season as they won for a seventh time from eight games.
The foundations of the victory at Ewood Park were laid in a frantic opening 18 minutes, with Reading going 3-1 up, thanks to goals from Yakou Meite -- clocked as the fastest in the club's history -- Michael Olise and Josh Laurent.
Adam Armstrong had made it 1-1 and then got Blackburn back in it in the second half, but Lucas Joao killed the game in the final 10 minutes.
Swansea was the big mover on the day as it climbed into the top two with a 2-0 home win over Stoke, with goals from Jay Fulton and Kasey Palmer.
Kenny McLean's late strike kept Norwich's good run of form going as it drew 1-1 at Brentford and Middlesbrough scored two late goals to beat Coventry 2-0.
Valerien Ismael made the perfect start as Barnsley's manager after leading his new side to a 3-0 victory over 10-man QPR at Oakwell.