Roger Schmidt's men went to the Veltins Arena on the back of Tuesday's agonising penalties defeat to Atletico Madrid in Europe's elite club competition, but that result seemingly had little effect on their state of mind as thoughts switched back to domestic matters.
Schalke were lively during the early exchanges, with Max Meyer and Leroy Sane looking particularly creative, but the hosts were ultimately made to rue not being clinical enough in front of goal.
Karim Bellarabi fired Leverkusen into the lead with an emphatic finish from a tight angle 10 minutes before the break and, although Jefferson Farfan made his return after almost a year out towards the end, Schalke never found a way past Bernd Leno.
The 1-0 defeat leaves Schalke five points behind fourth-placed Borussia Monchengladbach, who Leverkusen leapt above as a result of their victory.
Dortmund were comprehensively beaten 3-0 at home by Juventus in the Champions League on Wednesday, but got back to winning ways at Hannover, coming away with a 3-2 victory.
Pierre-Emerick Aubameyang put Dortmund ahead in the 19th minute before Hannover were level just after the half-hour through Lars Stindl.
A red card for former Dortmund midfielder Leonardo Bittencourt gave the visitors the upper hand soon after the break and Shinji Kagawa swiftly retook the lead for Jurgen Klopp's men.
Aubameyang then headed home Kagawa's cross to effectively secure the points – Stindl's late stunner doing little to ease pressure on under-fire Hannover coach Tayfun Korkut.
In the race for European places, Augsburg suffered their second successive league defeat and were left six points behind Gladbach, this time losing 2-0 at Freiburg, who moved out of the relegation zone as a result.
Rock-bottom Stuttgart gave their survival hopes a boost with a 3-1 win over Eintracht Frankfurt and fellow strugglers Paderborn drew 0-0 with visitors Hoffenheim.
The day's only other contest saw Werder Bremen leave Cologne with a 1-1 draw in their mid-table clash.
