And goals from Shkodran Mustafi, Pierre-Emerick Aubameyang and Henrikh Mkhitaryan saw Wenger to number 700, while Troy Deeney - who accused Arsenal of lacking "cojones" earlier in the season - had a penalty saved by Petr Cech.
After Deeney's penalty miss, Mkhitaryan added a third when he shot past Karnezis following Aubameyang's pass for his first league goal for the Gunners.
Arsenal won 2-0 in Italy last week and will be confident of securing their place in the Europa League quarter-finals later this week.
Arsenal return to action on Thursday night when they play Milan in the return leg of their Europa League tie.
Watford's chance to reduce the deficit from the spot came two minutes later, when Ainsley Maitland-Niles clumsily left his body in the path of Pereyra to go tumbling over.
"Then we can discuss how the team plays or something else, but I find that the criticisms that fall on Arsene on a personal level are hard to accept".
Arsenal boss Arsene Wenger, in his post-match interview to Arsenal Media, expressed, "Petr Cech shows a little bit how quickly things change in football".
Mustafi's goal similarly marked another milestone for the Gunners as the German defender scored Arsenal's 1,000th home goal of the Premier League era. "Fantastic motivation, fantastic desire and remarkable intelligence". "It was not as easy a game as the score says".
Ozil became the fastest player to reach 50 assists in the premier league. That kept us out of trouble.
Fair play to Deeney for fronting up when he knew he would get a lot of abuse for missing the penalty.
"But it was a big week and a big step forward to finish the season on a high, try to win the remaining games and see how far we can get". They face Stoke on April 1st, in their first game back after the worldwide break.