The visitors have succumbed to two successive defeats, meanwhile, and are edging closer to the bottom three.
Match preview
After comfortably securing Champions League qualification by finishing third in Gerardo Seoane's first season, the 43-year-old endured a nightmare start to his second campaign at BayArena.
Leverkusen meekly fell to their fifth defeat in eight league games away to Bayern Munich last Friday, before they were beaten 2-0 by Porto in Europe in midweek, leading to the former Young Boys boss being relieved from his duties as many had expected to happen even sooner.
The club have already found Seoane's successor in the shape of former Real Madrid and Liverpool midfielder Xabi Alonso, who has been handed a two-year contract in his first top-flight managerial role, having previously coached Real Sociedad's B team for three years.
Leverkusen's result in Portugal could have been very different had Patrik Schick converted a penalty on the stroke of half-time, but the Czech Republic international's effort from 12 yards was saved by Diogo Costa, whose side went on to score two goals in the last 20 minutes of the match.
The Black and Reds do still have a chance of reaching the knockout stages given that they are level on points with Porto and Atletico Madrid in Group B, but they must sort out their league form as a matter of priority, as last weekend's defeat in Bavaria has left them second bottom in the table.
Beating Schalke on Saturday would ensure that they at least move themselves outside of the automatic relegation positions, with Alonso hoping to make an immediate impression in his first match in charge.
Schalke, meanwhile, would have been kicking themselves to lose 3-2 at home to Augsburg last weekend.
Frank Kramer's side worked so hard to retrieve the match from falling two goals down in the early stages, with Simon Terrode and Tom Krauss scoring either side of the break to level the proceedings at Veltins-Arena.
Kramer and his players' eyes must have lit up when Augsburg were reduced to 10 men following Mergim Berisha's dismissal for a second bookable offence with 20 minutes remaining, but Andre Hahn's late winner stole all three points for the visitors.
As such, a defeat in Leverkusen on Saturday would guarantee that Schalke fall into the bottom three, with any positive result for Stuttgart at home to Union Berlin the following day meaning they would fall into the automatic relegation places.
From there, it may prove difficult to get out of them, making Saturday's trip to Leverkusen an extremely important one in shaping Die Konigsblauen's season.
Bayer Leverkusen Bundesliga form:
L
W
L
D
D
L
Bayer Leverkusen form (all competitions):
L
D
W
D
L
L
Schalke 04 Bundesliga form:
D
L
D
W
L
L
Team News
Leverkusen are set to remain without Karim Bellarabi, Florian Wirtz, Exequiel Palacios and Andrey Lunev through injury.
Jeremie Frimpong was sent off in Portugal in midweek but should retain his place in the starting XI - especially with him being unavailable for the return fixture on Wednesday - while Mitchel Bakker, Sardar Azmoun and Kerem Demirbay may come into the side with Alonso likely to favour more technically accomplished players.
Schalke have suffered the cruel blow of losing Sepp van den Berg to a serious knee injury, with the Liverpool loanee unlikely to play again before next month's World Cup begins.
Leo Greiml replaced the 20-year-old against Augsburg last week and is likely to do so from the start in Leverkusen on Saturday, especially with Cedric Brunner and Marcin Kaminski joining van den Berg on the sidelines at present.
Bayer Leverkusen possible starting lineup:
Hradecky; Frimpong, Tah, Tapsoba, Bakker; Demirbay, Aranguiz; Diaby, Azmoun, Hudson-Odoi; Schick
Schalke 04 possible starting lineup:
Schwolow; Matriciani, Greiml, Yoshida, Ouwejan; Krauss, Flick; Drexler, Zalazar, Bulter; Terrode
We say: Bayer Leverkusen 3-1 Schalke 04
We expect Leverkusen to put their recent woes behind them to some extent by claiming a second league win of the season on Saturday, especially with a new manager to impress.
Schalke look set for a long, difficult season ahead of them and there is little doubting the hosts' superiority in terms of their individual abilities.