Just the fourth time that the club has reached the last-eight in Europe, the Warriors know that victory will see them write their own piece of Glasgow rugby history by becoming the first group to ever reach the final four of a European competition.
Johnny Matthews returns to the starting XV after missing out on the visit to Pretoria, with the club's top try-scorer in 2021/22 joining Jamie Bhatti and Zander Fagerson in the front row.
An unchanged second-row sees Robert Harley and Richie Gray continue their partnership, bringing in excess of 600 career matches worth of combined experience to proceedings.
Ally Miller comes into the back-row in place of the injured Rory Darge, who is expected to be out for up to 12 weeks due to a knee injury, to join captain Ryan Wilson and number eight Jack Dempsey.
Behind the scrum, Ross Thompson comes into the lineup at fly-half, with Ali Price starting at scrum-half for the fourth match in succession.
Sam Johnson is promoted from the bench after starting amongst the replacements in Pretoria, joining fellow Scotland international Sione Tuipulotu in the centre.
The back three is unchanged, meaning Ollie Smith continues at full-back after scoring last time out, with Josh McKay and Cole Forbes lining up on the wings.
Fresh from signing his first professional contract with the club earlier in the week, Gregor Brown is in line to make his first Glasgow Warriors appearance in 14 months after being named amongst the replacements for tomorrow night's clash in France.
George Turner rotates to the bench after starting last time out, where he joins Simon Berghan and Nathan McBeth - the latter included in a European matchday squad for the first time - as the front-row cover.
Lewis Bean returns to Glasgow action after helping the British Army to victory in the Babcock Trophy at Twickenham last weekend, whilst Kiran McDonald wears the number 20 jersey in a six-two split on the bench.
Jamie Dobie and Domingo Miotti complete the matchday 23, with Argentina fly-half Miotti set for his European debut in Glasgow Warriors colours.
Speaking following selection, Head Coach Wilson told glasgowwarriors.org: "After two tough league matches we resume our European campaign and look to build on our good performance against Newcastle.
"Lyon are a side who have a number of threats across the park and are very consistent at home.
"We want to be playing at this level and testing ourselves against the best sides in Europe and this weekend's game gives us that chance.
"Returning from South Africa we've had a good week of training and we're looking forward to taking on Lyon tomorrow evening."
15 Ollie Smith
14 Josh McKay
13 Sione Tuipulotu
12 Sam Johnson
11 Cole Forbes
10 Ross Thompson
9 Ali Price
1 Jamie Bhatti
2 Johnny Matthews
3 Zander Fagerson
4 Robert Harley
5 Richie Gray
6 Ryan Wilson (Captain)
7 Ally Miller
8 Jack Dempsey
Substitutes
16 George Turner
17 Nathan McBeth
18 Simon Berghan
19 Lewis Bean
20 Kiran McDonald
21 Gregor Brown
22 Jamie Dobie
23 Domingo Miotti
Unavailable for selection: Fraser Brown, Sebastian Cancelliere, Scott Cummings, Rory Darge, Matt Fagerson, Walter Fifita, Tom Gordon, George Horne, Rufus McLean, Kyle Steyn, Duncan Weir