Both sides secured Champions League football last season, but will hope to challenge Bayern Munich for the title this time around.
While Dortmund only finished eight points behind champions Bayern in the end, in truth that gap flattered Der BVB somewhat due to the Bavarians taking their foot off the gas once they had wrapped up a 10th successive league title.
Dortmund, of course, were the last team to break Bayern's dominance in the Bundesliga, with current Liverpool boss Jurgen Klopp guiding his former club to two successive league titles in 2011 and 2012.
There have been a couple of near misses since those glory years, with Edin Terzic hoping to become the man to break the cycle having been reappointed as manager this summer.
The 39-year-old guided Dortmund to a DFB-Pokal triumph as caretaker boss in the 2020-21 season, and he has been handed the reins on a permanent basis this time around after Marco Rose departed the club by mutual consent.
BVB comfortably swept aside third-tier outfit 1860 Munich in the first round of the DFB-Pokal last Friday, with first-half strikes from Donyell Malen, Jude Bellingham and debutant Karim Adeyemi making the second-half something of an early season stroll.
Saturday evening, on the other hand, is likely to be be anything but that against a Leverkusen side which blitzed them 5-2 at Westfalenstadion in February earlier this year.
Indeed, Leverkusen massively kicked on in Gerardo Seoane's first season in charge of the club, comfortably securing third spot to qualify for the Champions League for the first time in three seasons.
The former Young Boys boss has made Die Werkself a thrilling side to watch, with their impressive goals for tally of 80 only bettered by Bayern and Dortmund last season.
Leverkusen's competitive season did not get off to the best start last weekend, either, with an embarrassing 4-3 defeat at the hands of third tier side SV Elversburg in the first round of the DFB-Pokal.
Seoane's side will need to be much more defensively astute against Dortmund on Saturday, otherwise their league campaign is almost certain to begin on a bad note, too.
Dortmund will be without new signing Sebastien Haller as the forward recovers from having a testicular tumour removed.
The club are seeking a short-term replacement for the Ivory Coast international, who was signed for around £28m to help fill the goalscoring void of Erling Braut Haaland.
In the meantime, 17-year-old Youssoufa Moukoko could be handed a chance to lead the line after starting in last weekend's cup win against 1860 Munich.
With support from Malen, captain Marco Reus and Adeyemi, who will make his first Bundesliga start here, Terzic's side do not look short of goals even without a conventional striker.
At the back, meanwhile, Nico Schlotterbeck is in line for his league debut, but he will not be joined by fellow new signing Niklas Sule after the Germany international limped off with a muscle strain against 1860 Munich.
Leverkusen, meanwhile, will travel without their teenage sensation Florian Wirtz as he continues to recover from the cruciate ligament rupture that he sustained last season.
Wirtz could be out of action for another couple of months at least, heaping pressure on Sardar Azmoun to deliver in the number ten role after a relatively slow start to life in Germany since moving from Zenit Saint Petersburg in January.
Hlozeck should make his first league start for the club after scoring in his side's loss to Elversburg, with the contributions of Moussa Diaby and Patrik Schick in attack likely to be crucial to any success that Die Werkself may have this season.
Amine Adli remains sidelined with a torn tendon.
Borussia Dortmund possible starting lineup:
Kobel; Meunier, Hummels, Schlotterbeck, Guerreiro; Bellingham, Dahoud; Adeyemi, Reus, Malen; Moussoko
Bayer Leverkusen possible starting lineup:
Hradecky; Frimpong, Kossounou, Tapsoba, Bakker; Aranguiz, Andrich; Diaby, Armoun, Hlozek; Schick
We say: Borussia Dortmund 3-2 Bayer Leverkusen
We expect to see a highly entertaining, high-scoring affair between two attacking teams on Saturday.
Both meetings saw seven goals scored at either end last season, but we expect the hosts to just edge it having looked more ready for the new season in the DFB-Pokal last weekend.
For data analysis of the most likely results, scorelines and more for this match please click here.
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