Ali Price assumes the captaincy as Kyle Steyn drops out due to injury, with last weekend's Player of the Match George Horne similarly rotating out of the matchday 23.
An unchanged front-row sees Jamie Bhatti and Zander Fagerson pack down as the starting props, as Fraser Brown continues at hooker after his two tries in last week's win over Cardiff.
Richie Gray and Scott Cummings continue their partnership in the second-row, the latter currently leading the URC in lineout steals with three to date.
Jack Dempsey is the only member of the back-row to retain his place from last weekend's victory at Scotstoun, as Tom Gordon replaces the injured Rory Darge at openside and Gregor Brown comes in at blindside after a knock to Matt Fagerson in midweek.
Tom Jordan makes his third successive start at fly-half as he partners skipper Price in the half-backs, the former Ayrshire Bull sitting in the league's top 10 for offloads after the first two rounds.
Sam Johnson comes into the starting lineup to make his first appearance of the season at inside centre, partnering Scotland team-mate Sione Tuipulotu in the midfield.
Steyn's place on the wing goes to Rufus McLean, who returns from an off-season injury to join a back-three rounded out by Sebastian Cancelliere and full-back Cole Forbes.
On the bench, double centurion Ryan Wilson is in line for his first outing of the season, having been named as part of a six-two split of forwards and backs by the club's coaching team.
Simon Berghan and Sean Kennedy are similarly in line for their first action of the campaign, with Kennedy set for his first Glasgow Warriors appearance since April's victory over Zebre Parma at Scotstoun.
George Turner and Oli Kebble join Berghan as the front-row replacements, whilst JP du Preez continues in the matchday 23 after making his competitive debut for the club last weekend.
Sintu Manjezi wears the number 20 shirt as he covers both the second and back-rows, with Argentinian fly-half Domingo Miotti completing the cohort of replacements.
Speaking following selection, Franco Smith told glasgowwarriors.org: "Last weekend's performance against Cardiff was another step forward in our journey - our systems clicked and we won playing our brand of rugby.
"Tomorrow we want to make another step forward when we take on an experienced Ospreys side.
"It's great to be able to bring Sam, Rufus and Gregor into the starting XV. They alll have worked hard in training and have earned their chance to pull on the jersey tomorrow afternoon.
"Ospreys have threats across the park and once again we will need to be ruthless in the contact area and clinical in attack in Swansea tomorrow."
15 Cole Forbes
14 Sebastian Cancelliere
13 Sione Tuipulotu
12 Sam Johnson
11 Rufus McLean
10 Tom Jordan
9 Ali Price (Captain)
1 Jamie Bhatti
2 Fraser Brown
3 Zander Fagerson
4 Scott Cummings
5 Richie Gray
6 Gregor Brown
7 Tom Gordon
8 Jack Dempsey
Substitutes
16 George Turner
17 Oli Kebble
18 Simon Berghan
19 JP du Preez
20 Sintu Manjezi
21 Ryan Wilson
22 Sean Kennedy
23 Domingo Miotti
Unavailable for selection: Rory Darge (ankle), Allan Dell (calf), Jamie Dobie (hamstring), Matt Fagerson (rib), Huw Jones (back), Nathan McBeth (knee) Ally Miller (back), Enrique Pieretto (shoulder), Kyle Steyn (hamstring), Max Williamson (shoulder)