The Warriors, who have already booked their place in the GUINNESS PRO12 play-offs, take on fourth-placed Ospreys in the penultimate game of the regular season as they try and secure a home play-off for the second consecutive year.
Weir replaces Finn Russell in the Number 10 shirt, which is the only change to the back-line which started the 31-13 win over Connacht in Galway almost a fortnight ago.
In the forwards Ryan Grant comes in for Jerry Yanuyanutawa at loose-head, Pat MacArthur replaces Fraser Brown at hooker and Jon Welsh continues at tight-head.
Tim Swinson comes in for Leone Nakarawa in the second-row and he'll partner Jonny Gray in the engine room.
In the back-row Rob Harley and Chris Fusaro continue at blind-side and open-side respectively, while Josh Strauss replaces Adam Ashe at Number 8 and captains the side.
Following the conclusion of his suspension Ryan Wilson is named amongst the replacements, along with Fraser Lyle who could make his first appearance since representing Scotland 7s in Hong Kong and Tokyo.
Glasgow Warriors head coach Gregor Townsend said: "We're well aware of the importance of tomorrow night's game and what it means to everyone associated with the club.
"Securing our place in the play-offs is a massive achievement, but we're now playing for home advantage and we know these next two games are crucial to achieving that outcome.
"Ospreys are only four points behind and they too are playing for a home play-off, so we're expecting an extremely tough game at the Liberty Stadium.
"They have played at a consistently high level throughout the season and have a good balance in their play - a strong, aggressive defence allied to an excellent attacking game.
"We will need to put in one of our best performances of the season to come away with a positive result."
Glasgow Warriors team to play Ospreys, GUINNESS PRO12, Liberty Stadium, Friday 8 May (kick-off 7.35pm) - live on BBC Two Wales and BBC Red Button:
15. Stuart Hogg
14. Tommy Seymour
13. Richie Vernon
12. Peter Horne
11. Niko Matawalu
10. Duncan Weir
9. Henry Pyrgos
1. Ryan Grant
2. Pat MacArthur
3. Jon Welsh
4. Tim Swinson
5. Jonny Gray
6. Rob Harley
7. Chris Fusaro
8. Josh Strauss (Captain)
Replacements
16. Fraser Brown
17. Gordon Reid
18. Euan Murray
19. Leone Nakarawa
20. Ryan Wilson
21. Lee Jones
22. Fraser Lyle
23. Peter Murchie
Not available due to injury: Alex Allan (shoulder), Adam Ashe (neck), Mark Bennett (shoulder), Mike Cusack (foot), Alex Dunbar (knee), Tyrone Holmes (knee), Sean Maitland (shoulder) and DTH van der Merwe (hand).
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