Watford substitute Yaser Asprilla snatched a late winner to deny Danny Rohl a point in his first game as Sheffield Wednesday boss.
The Colombian teenager had only been on the pitch for four minutes when he cut in from the right and rifled his finish across Cameron Dawson.
Dawson had barely been tested up to that point, with the visitors largely keeping Watford at bay and creating the better chances.
But Wednesday remain bottom of the Championship table and winless this season, while Watford's first victory in six games lifts them to 19th place.
Rohl rang the changes in his first game after succeeding Xisco Munoz, with only three players retained in the starting line-up from their 0-0 draw with Huddersfield a fortnight ago.