With Leverkusen seeking a seventh successive league win in the face of opposition that had recently beaten Bayern Munich and Frankfurt, they dominated much of the first half.
Patrik Schick saw a shot blocked in only the seventh minute before Piero Hincapie sliced a shot narrowly wide of Robin Zentner’s goalmouth.
Florian Wirtz always looked menacing too, and he took a shot from distance that would have crept inside Zentner’s left-hand post, but for his fingertips.
And Alex Grimaldo tried his luck too, with a shot from the edge of the box, once more forcing Mainz’s stopper into action.
But any frustration Grimaldo felt was translated into a marvellous opening goal early in the second half. A foul from Stefan Bell on the cusp of the box allowed the Spaniard to size up the target and strike a beautiful free-kick inside the stranded Zentner’s right-hand post.
Leverkusen continued to probe in search of what would surely be a decisive second, and another long-range shot from Wirtz tested Zentner, with Mainz’s keeper tipping over the bar.
But it wasn’t all one-way traffic, and when Nelson Weiper received a pullback in the box right in front of goal, his low shot towards the bottom-right corner on the angle lacked any real conviction, allowing Matej Kovar to get down and hold the ball gratefully.
Jeremie Frimpong could have put the game beyond doubt with about 20 minutes remaining, with a counter-attack seeing him burst into the box after a fine solo run. He looked up and tried to find the bottom-right corner, but Zentner was one more sharp to deny him.
This wasn’t a stroll in the park for Leverkusen, but they were ultimately well worth the victory which sees them moving to within a point of leaders Bayern Munich for the time being.
As for Mainz - who saw head coach Bo Henriksen sent off in injury time - the gap between themselves and the top-four could be five points this time tomorrow after only their second defeat on the road all season.
Flashscore Man of the Match: Alex Grimaldo (Bayer Leverkusen)
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Other Bundesliga results:
Eintracht Frankfurt 4-1 Freiburg
