German champions Bayern thrashed Barcelona 8-2 to book a place in the semi-finals, while Lyon - seventh-placed finishers in Ligue 1 - stunned Manchester City with a 3-1 win.
The winners of this tie will face Paris Saint-Germain in Sunday's final.
Even before crushing Barcelona, Bayern were already the favourites of many to go all the way in this year's competition and lift the European Cup for a sixth time.
After becoming the first side to score eight goals in a Champions League knockout match, it is now tough to see exactly which team will stop them from winning a famous treble.
Nineteen teams have tried and failed to stop the Bavarian giants from winning in a run stretching back to February 16.
In fact, going further back, Hansi Flick's men have now won 24 of their last 25 matches in all competitions, the exception being a stalemate with fellow semi-finalists RB Leipzig.
The manner of their crushing win over European heavyweights Barca really was one of those 'where were you?' moments, with six different players getting on the scoresheet.
Even more impressive than that, all eight goals were assisted by a different player, showing just how much attacking depth Bayern have in their ranks.
As witnessed in the last round against a much-fancied Man City side, though, Lyon cannot be written off in this intriguing final-four showdown in Lisbon.
Incredibly, Lyon have not won consecutive Champions League matches in a single campaign since the 2011-12 season when defeating Dinamo Zagreb and APOEL.
Les Gones also knocked out Italian champions Juventus in the last 16, however, and will enter this match full of confidence.
In what could be a good omen for Lyon - and they will no doubt take whatever they can - Bayern have failed to progress from each of their last four semi-finals.
Bayern came out on top when the sides met at this stage in the 2009-10 semis, albeit with that tie being played over two legs, unlike this one-off clash on neutral soil.
In a unique campaign that has provided many surprises, Lyon will be hoping for one more massive twist as they look to overcome the continent's most in-form side.
Lyon Champions League form: WLDWLW
Lyon's form (all competitions): WLLLLW
Bayern Munich's Champions League form: WWWWWW
Bayern Munich's form (all competitions): WWWWWW
Bayern defender Benjamin Pavard returned to light training on Monday and is back in contention for this semi-final.
Robert Lewandowski has scored in eight consecutive Champions League appearances for Bayern – only Ruud Van Nistelrooy in 2003 (9) and Cristiano Ronaldo in 2018 (11) have scored in more successive matches in the competition's history.
As for Lyon, Dembele will be pushing for inclusion up top after his double from the bench against City, which could mean Karl Toko Ekambi dropping out.
However, Garcia has found a system that works well, with Ekambi and Memphis Depay giving the French side a platform to hit sides on the counter.
Lyon possible starting lineup:
Lopes; Marcelo, Denayer, Marcal; Dubois, Caqueret, Guimaraes, Aouar, Cornet; Ekambi, Memphis
Bayern Munich possible starting lineup:
Neuer; Kimmich, Boateng, Alaba, Davies; Goretzka, Thiago; Gnabry, Muller, Coman; Lewandowski
We say: Lyon 1-3 Bayern Munich
No team in Champions League history have won their first nine games in a campaign, something that Bayern can achieve with another victory on Wednesday. Lyon may have knocked out Juventus and Man City, but Flick's rampant side have been nothing short of phenomenal either side of the coronavirus-enforced hiatus and are big favourites to prevail here.