Amen Abdi’s second-half strike denied Wanderers a point on the road, after Marvin Sordell claimed the Whites’ only goal on his return to Vicarage Road.
Referee James Alcock pointed to the spot on 32 minutes after Sam Ricketts was fouled in the area by Daniel Pudil, and the former Watford man sent Manuel Almunia the wrong way from 12 yards.
But Vydra replied four minutes later before in the second half Abdi finished from the edge of the area to seal victory for the hosts.
Wanderers made one change from the FA Cup fourth round defeat to Everton, with Adam Bogdan returned to the starting line-up. There were also places on the bench for January signings Craig Davies, Craig Dawson and Steve De Ridder.
The Trotters were the quickest out of the traps and put pressure on the Hornets’ back four early on, as Darren Pratley saw the game’s first opportunity go narrowly over the bar.
Wanderers, however, almost found themselves behind after 10 minutes. Troy Deeney burst through on goal but his low drive was superbly repelled by Bogdan.
The Whites continued to enjoy the large share of possession and both full-backs pushed forward to assist, as first Marcos Alonso had a close rang effort blocked in front of goal before Chris Eagles found space in the box to turn and fire a shot just over the top.
The hosts rarely threatened the Bolton goal, but the Hornets were always a threat on the counter-attack as Nathaniel Chalobah saw his chip from an acute angle go just over, before Sordell almost latched on to a Pratley through ball.
But the vocal travelling support were soon celebrating the opening goal on 32 minutes. Pratley was able to feed the marauding Ricketts, who powered his way into the area and was adjudged to have been brought down by Pudil.
Sordell, making his first return to Watford after departing the club 12 months ago, stepped up and continued his good scoring run by sending Almunia the wrong way.
But Watford were back on level terms just four minutes later. Tim Ream’s unfortunate slip allowed Matej Vydra to run through on goal and the Czech forward made no mistake from the right channel to slot past Bogdan.
Conceding a goal prior to the interval didn’t deter the Trotters, who started the second half positively. Jay Spearing picked the ball up inside the centre circle and ran 30 yards before unleashing a low shot which was superbly saved by Almunia.
Watford almost replied immediately courtesy of Abdi, but his close-range strike went narrowly wide of Bogdan’s near post.
The width of a goalpost then denied the Trotters soon after. Chung-Yong Lee was able to weave his way into the Watford area and the South Korean slid a ball into the feet of Sordell, but the forward could only hit the post from a tight angle.
Both sides enjoyed stints with the ball, and Ream’s goal-saving block denied Vydra, but Watford would eventually take the lead on 75 minutes.
Vydra was fed the ball inside the Bolton area and the forward laid a pass back to Abdi who managed to find a gap through the Whites’ defence to slot the ball into the corner.
The manager reacted immediately by making a triple substitution, introducing De Ridder, Craig Davies and Kevin Davies - his 400th appearance for the club.
Craig Davies went close, but the Trotters were unable to find an equaliser in Hertforshire.
Watford: Almunia, Hall, Deeney, Doyley, Pudil, Vydra, Abdi, Cassetti, Battocchio (Eustace 90), Chalobah (Hogg 84) Ekstrand (Nosworthy 78) (Unused subs: Bond, Murray, Geijo, Forestieri)
Wanderers: Bogdan, Alonso, Ream, Knight, Ricketts, Spearing, Vela (K Davies 75), Pratley, Eagles (De Ridder 75), Chung-Yong, Sordell (C Davies 75) (Unused subs: Lonergan, Ngog, Wylde, Dawson)