Nathan Tella headed Xabi Alonso’s side into a first-half lead, nine minutes after Wolfsburg defender Moritz Jenz had been sent off for his second yellow card, and Florian Wirtz ensured maximum points with a late second.
Leverkusen extended their unbeaten run in the Bundesliga this season to 25 matches and notched their sixth straight league win to stay well in front of Bayern Munich, who thrashed Mainz 8-1 on Saturday.
Eintracht Frankfurt consolidated in sixth place after hitting back to win 3-1 at home against nine-man Hoffenheim.
United States defender John Brooks headed Hoffenheim into an early lead, but was shown a straight red card for his challenge on Omar Marmoush before Frankfurt equalised through on-loan Leeds centre-back Robin Koch.
Second-half goals from Dina Ebimbe and Mario Gotze put Frankfurt in control and Hoffenheim were then reduced to nine men when Ozan Kabak received his second yellow card.
Freiburg followed up their midweek Europa League win against West Ham with their first Bundesliga victory in seven matches, triumphing 2-1 at Bochum.