The home team recorded their first win of the season as they proved too strong for last year's runners-up in their Bundesliga opener
Leverkusen started the match as favourites, but Mainz grabbed the lead after 32 minutes of play. Shot-stopper Fabian Giefer failed to clear the ball and passed the ball straight into the path of Sami Allagui, who had no trouble finding the net.
The away side weren't too impressed and came close to levelling the score on a number of occasions, but Mainz goalkeeper Heinz Muller proved to be too much of an obstacle.
The hosts decided the game late in the second half when Omer Toprak was unable to clear a cross from Marco Caligiuri and beat his own keeper.
Mainz have an away match against Freiburg next week, while Leverkusen host Werder Bremen on matchday two.