Josh Strauss starts at Number 8 after returning from injury, while Ryan Wilson moves to openside flanker and Rob Harley completes the back-row at blindside.
Both Ali Price and Rory Clegg make their first starts of the season in the half-back positions, while Peter Horne shifts to inside centre to accompany Grigg who will wear 13.
Lee Jones also makes his first start of the campaign on the left wing, Stuart Hogg starts at full-back and last week's man of the match Tommy Seymour will look to continue his try scoring form on the other flank having scored six in the opening two games.
In the front-row, Zander Fagerson joins Gordon Reid and Fraser Brown and behind them is Tim Swinson, who has also scored in the opening two matches, accompanying captain Jonny Gray in the second-row.
Olympic Silver Medalist Mark Bennett is involved for the first time since returning from the Rugby 7s in Rio and he'll hope to make an impression from the bench.
Greg Peterson, Grayson Hart and Rory Hughes will also play their first competitive rugby of the season if they come on and they are joined by Pat MacArthur, Alex Allan, Sila Puafisi and Lewis Wynne to complete the replacements.
Glasgow Warriors head coach Gregor Townsend said: "Nick Grigg has worked very hard during pre-season and played well against Harlequins and Canada 'A' last month. He deserves his opportunity tomorrow.
"It's also great that we're able to welcome Josh Strauss and Mark Bennett back into the squad. Josh has recovered from an ankle injury and Mark came back from Rio fit and hungry and it didn't take him long to integrate himself back into the group.
"Cardiff have started the season very strongly and can score tries from anywhere. They have had excellent wins against Edinburgh and Munster and we're going to need to improve defensively to get a positive result at the Arms Park tomorrow night."
Glasgow Warriors team to play Cardiff Blues at BT Sport Arms Park, Friday 16 September (kick-off 7pm):
15. Stuart Hogg
14. Tommy Seymour
13. Nick Grigg
12. Peter Horne
11. Lee Jones
10. Rory Clegg
9. Ali Price
1. Gordon Reid
2. Fraser Brown
3. Zander Fagerson
4. Tim Swinson
5. Jonny Gray (Captain)
6. Rob Harley
7. Ryan Wilson
8. Josh Strauss
Replacements
16. Pat MacArthur
17. Alex Allan
18. Sila Puafisi
19. Greg Peterson
20. Lewis Wynne
21. Grayson Hart
22. Mark Bennett
23. Rory Hughes
Not available due to injury: Adam Ashe (hip / foot), Scott Cummings (shoulder), Simone Favaro (shoulder), Chris Fusaro (knees), Ryan Grant (back), Sam Johnson (shoulder), Sean Lamont (foot), Henry Pyrgos (knee) and D'arcy Rae (back).
Guinness PRO12 Warriors News
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