Xabi Alonso's side got the better of Marseille 2-1 in their penultimate warm-up match, while the Hammers were seen off 3-1 by French outfit Rennes.
Match preview
Resisting interest from Tottenham Hotspur to continue in the BayArena hotseat, Leverkusen head coach Alonso oversaw Die Werkself's eye-catching run to the Europa League semi-finals last year, following their short-lived bid at Champions League stardom.
A sixth-placed finish in the Bundesliga offered Leverkusen a route back into Europe's secondary competition - where West Ham could potentially test their continental mettle - but the hosts' pre-season preparations began in dismal fashion with back-to-back defeats to Paderborn and Real Sociedad.
However, the third time was the charm for Leverkusen, who edged past Marseille 2-1 on Wednesday thanks to first-half strikes from Jonathan Tah and Nadiem Amiri, before Francois-Regis Mughe made things interesting 13 minutes from time.
Before commencing their new Bundesliga campaign, Leverkusen will return to competitive duties against fourth-tier Teutonia Ottensen in the first round of the DFB-Pokal next weekend, which precedes an intriguing top-flight opener versus RB Leipzig seven days later.
A significant period of change has occurred at BayArena this summer, as the long-serving Kerem Demirbay and Karim Bellarabi have followed Aston Villa new boy Moussa Diaby out of the door, but Alex Grimaldo, Granit Xhaka, Victor Boniface and Jonas Hofmann represent a quartet of astute acquisitions.
While the West Ham faithful can empathise when it comes to losing long-serving players, the Irons are yet to bring in a single marquee addition to their squad, only capturing Irish starlet Sean Moore from Cliftonville before embarking on a period of goal-laden friendlies.
David Moyes's Europa Conference League winners sealed a trio of successive wins over Boreham Wood, Perth Glory and Tottenham Hotspur before being pegged back on two occasions in a 2-2 stalemate with Dagenham & Redbridge, but a quick stopover in Brittany did not to go to plan.
Indeed, West Ham were ostensibly set to come away from Rennes' turf with a draw after Tomas Soucek cancelled out Baptiste Santamaria's opener, but an Arnaud Kalimuendo strike and Angelo Ogbonna own goal inside the final 15 minutes condemned the Hammers to their first loss of the summer.
Moyes's side have just one shot at exhibition redemption on Saturday before their Premier League campaign kicks off with a trip to Bournemouth on August 12, prior to which Hammers fans will be demanding at least one new face through the door.
Leverkusen and West Ham have unsurprisingly never locked horns in competitive action before, but the German side have only ever won four of their 21 meetings with English clubs, overcoming Blackburn Rovers, Chelsea, Liverpool and Tottenham Hotspur on one occasion.
Bayer Leverkusen friendly form:
West Ham United friendly form:
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Team News
On Thursday morning, Leverkusen confirmed the permanent transfer of veteran midfielder Demirbay to Galatasaray, while in-demand right-back Jeremie Frimpong and Tottenham Hotspur-linked defender Edmond Tapsoba could also be on the move before the window slams shut.
However, the defensive duo were both in action against Marseille - where Robert Andrich also returned from a three-month layoff with a broken foot - but Sardar Azmoun (calf), Patrik Schick (groin) and Piero Hincapie (ankle) are all out of contention.
With Schick and Azmoun absent, the onus will be on new signing Boniface and Czech starlet Adam Hlozek to come up with the attacking goods, while the exciting Florian Wirtz could also come back into the first XI.
Meanwhile, West Ham's summer cull could soon continue with the transfer of misfiring striker Gianluca Scamacca to Inter Milan, although the ex-Sassuolo man still turned out for the final 20 minutes of their recent loss to Rennes.
However, Michail Antonio - who has also been tipped to head elsewhere this summer - has been granted additional time off following his exploits for Jamaica, and the same can be said for England's Under-21 European champion Ben Johnson.
Moyes is otherwise blessed with a fully-fit contingent and should put out a strong XI for West Ham's final tune-up fixture, but the up-and-coming Divin Mubama and Flynn Downes should still earn some minutes here.
Bayer Leverkusen possible starting lineup:
Hradecky; Tapsoba, Kossounou, Tah; Frimpong, Xhaka, Palacios, Grimaldo; Wirtz; Boniface, Hlozek
West Ham United possible starting lineup:
Fabianski; Coufal, Zouma, Aguerd, Emerson; Downes, Soucek, Paqueta; Bowen, Ings, Benrahma
We say: Bayer Leverkusen 2-1 West Ham United
Attacking absences have hit Leverkusen hard in pre-season, but Alonso's side should still make their forward forays count against a permeable West Ham backline - one which has not kept a single clean sheet in pre-season.
It may take some time for the hosts' summer arrivals to fully integrate with the rest of the squad, but we still expect Die Werkself to be the ones to end their pre-season on a high note.