Rennie used last weekend's victory over the Scarlets as an opportunity to rest several players and welcomes a dozen internationals back to his match day 23, as well as captain Callum Gibbins.
Adam Ashe is rewarded with his excellent form with a place in the back-row alongside Gibbins, with Matt Fagerson also returning.
Both Robert Harley and Jonny Gray missed Glasgow's victory over the Scarlets last weekend and are brought into the engine room for the trip to France.
Oli Kebble's performance off the bench at Scostoun last weekend made headlines and he starts this Saturday. D'arcy Rae keeps his spot at tight-head and they will both prop down either side of the returning Fraser Brown.
It's a brand new back-three. Stuart Hogg and Tommy Seymour come in after impressing in Scotland shirts this Autumn, while DTH van der Merwe is back having helped Canada qualify for the Rugby World Cup last month.
Peter Horne starts alongside Nick Grigg in midfield, while his brother George is joined at half-back by Adam Hastings.
Ali Price and Huw Jones are two more Scotland internationals who will look to make an impact off the bench when called upon.
Glasgow Warriors Head Coach Dave Rennie, said: "It's exciting to be back playing in Europe.
"We're really proud of our performances during the international window and to get 16 points against top opposition was really pleasing.
"We've picked a 23 based on form for both club and country and we're looking forward to the challenge Lyon will present."
15 Stuart Hogg
14 Tommy Seymour
13 Nick Grigg
12 Peter Horne
11 DTH van der Merwe
10 Adam Hastings
9 George Horne
1 Oli Kebble
2 Fraser Brown
3 D'arcy Rae
4 Robert Harley
5 Jonny Gray
6 Adam Ashe
7 Callum Gibbins (Captain)
8 Matt Fagerson
Substitutes
16 George Turner
17 Jamie Bhatti
18 Siua Halanukonuka
19 Tim Swinson
20 Chris Fusaro
21 Ali Price
22 Huw Jones
23 Nikola Matawalu
Not available due to injury: Zander Fagerson (ankle), Rory Hughes (shoulder), Sam Johnson (knee), Lee Jones (knee) and Lelia Masaga (calf)