Mainz almost scored their consolation in the dying minutes of the clash but Jean-Philippe Mateta's back-heel flick missed the target just wide.
With the win, Leipzig jump up to third whereas Mainz continue in 15th, only four points away from the drop zone.
"We played out many chances again and this time we turned them into a tangible reward. It was an overall very good performance," Leipzig's sporting director Markus Krosche said.
Elsewhere, Schalke suffered their second straight defeat as goals from Eduard Lowen, Noah Joel Sarenren Bazee and Sergio Cordova secured Augsburg their eighth win of the season. Cologne rallied back from two goals down in the injury time to force rivals Fortuna Dusseldorf to a share of the spoils.
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