Leverkusen and Wolfsburg staged an evenly balanced opening period but as both defenses neutralized all offensive action the spectators had to wait until the 25th minute before action on the pitch kicked off.
Karim Bellarabi brought down a long ball and danced through Wolfsburg's defense before slotting home the opener from inside the box.
After the break Wolfsburg assumed control as Maximilian Arnold's effort forced Leverkusen goalkeeper Lukas Hradecky into action in the 51st minute.
The "Wolves" created the next chance two minutes later after Felix Klaus pulled wide from the edge of the box.
The hosts relied on counter-attacks meanwhile Wolfsburg pressed forward to overcome Leverkusen's well-positioned defense.
However, Wolfsburg's efforts remained fruitless as clinical Leverkusen sealed the deal in the closing period after substitute Paulinho made the most of Kevin Volland's build-up work to make it 2-0 on the scoreboards.
With the result, Leverkusen reaped their first win after four winless games in a row to climb on the 8th place while Wolfsburg's winless streak extends to eight games to slip to the 10th position of the Bundesliga standings.
Elsewhere, ten-men Freiburg recorded their sixth win of the season after edging nine-men Eintracht Frankfurt on the sole goal from Nils Petersen, who marked his 11th goal of the campaign.
Both sides had to conclude the game with a reduced amount of players as Frankfurt's Gelson Fernandes was sent off after seeing his second yellow card in the first half before David Abraham saw a straight red card due to violent conduct against the Freiburg coach Christian Streich in the added time.
In the subsequent brawl, Freiburg's Vincenzo Grifo saw also a straight red card after attacking Abraham from the bench in the dying seconds of the game.
With the victory, Freiburg moved on the 4th place whereas Frankfurt dropped to the 9th position of the table.