The match marks the first match in the 150th anniversary series between the two sides, with Glasgow and Edinburgh having first met at Burnbank, home of Glasgow Academical RFC, in November 1872.
Warriors earned a bonus-point victory over Perpignan in last weekend's European Challenge Cup, and Smith has freshened up his side for the return to URC action.
Fraser Brown comes in at hooker to pack down between Jamie Bhatti and Murphy Walker.
Sintu Manjezi is promoted to the starting XV after coming off the bench last time out, as the South African joins Richie Gray in the engine room.
The back-row is unchanged from last week's win over Perpignan, meaning that Player of the Match Sione Vailanu continues at openside alongside Matt Fagerson and Jack Dempsey.
Behind the scrum, Tom Jordan comes in at number 10, partnering George Horne in the half-backs.
Stafford McDowall and Sione Tuipulotu combine in the midfield, the former coming into the squad after missing out on last weekend's match at Murrayfield.
Kyle Steyn returns with the skipper slotting in at wing in place of Rufus McLean, with Sebastian Cancelliere and Josh McKay completing an otherwise unchanged back-three.
On the bench, a six-two split of forwards and backs sees Cameron Neild return to the matchday 23 after missing out on last weekend's win, having made his club debut in the away victory over Bath at The Rec.
George Turner rotates to the bench after starting last Friday, with Nathan McBeth and Simon Berghan retaining their places in the matchday 23.
Similarly, Lewis Bean moves to the replacements to wear the number 20 jersey, joining JP du Preez amongst the cover in the pack.
Ali Price and Domingo Miotti complete the matchday squad, the latter set for his first experience of an 1872 Cup clash at Scotstoun.
Speaking following selection, Head Coach Franco Smith told glasgowwarriors.org: "Last weekend's win over Perpignan was another important step in our growth as a squad.
"To get the bonus-point win was pleasing, but we know that we can still be much better in our performance and in our processes across the pitch.
"Everyone involved with the club is looking forward to this match. Training this week has been highly competitive and has made this one of our toughest selections of the season to date.
"Edinburgh will provide a stern test for us, and we're prepared for a highly physical test across the next fortnight."
15 Josh McKay (20)
14 Sebastian Cancelliere (17)
13 Sione Tuipulotu (27)
12 Stafford McDowall (44)
11 Kyle Steyn (Captain) (55)
10 Tom Jordan (9)
9 George Horne (89)
1 Jamie Bhatti (76)
2 Fraser Brown (130)
3 Murphy Walker (11)
4 Sintu Manjezi (10)
5 Richie Gray (91)
6 Matt Fagerson (84)
7 Sione Vailanu (5)
8 Jack Dempsey (27)
Substitutes
16 George Turner (84)
17 Nathan McBeth (10)
18 Simon Berghan (18)
19 JP du Preez (9)
20 Lewis Bean (24)
21 Cameron Neild (1)
22 Ali Price (117)
23 Domingo Miotti (12)
Unavailable for selection: Scott Cummings (foot), Rory Darge (ankle), Allan Dell (calf), Zander Fagerson (hamstring), Tom Gordon (calf), Oli Kebble (shoulder), Jack Mann (head), Enrique Pieretto (chest), Alex Samuel (back), Ross Thompson (ankle), Ryan Wilson (knee)