Watson – who becomes the capital side’s 33rd centurion – is named in a starting XV that includes five changes to the side that faced Ulster a fortnight ago.
A revamped centre partnership sees James Johnstone and Chris Dean return from injury to start, while Simon Hickey and Dougie Fife are selected at stand-off and wing respectively in the place of injured duo Jaco van der Walt and Damien Hoyland.
John Barclay, the 71-times capped back-row, is named at blindside flanker in place of Magnus Bradbury – who drops to the bench – in the only alteration to the pack.
Ahead of the fixture, Head Coach Richard Cockerill, said: “We have to go there and win with a bonus-point for a chance to qualify for Europe. Glasgow are a good side and right now they are playing with plenty of confidence.
“They are in the top two in their pool, and they may well finish first for the second straight year, because they’ve got very good players.
“But we know we can compete at that level and we’ve shown that this season. But we’ve got to do it again. We’re going to Scotstoun to win.
“We’ve had a good run against them and we’ve to keep believing in ourselves. We’ll go to play our game and we’ll make sure we impose ourselves on them. I’m sure they are saying the same and we’ll both go out to make it a proper derby day again.”
Duhan van der Merwe – twice a scorer in December’s 1872 Cup first leg victory at BT Murrayfield – is partnered by Fife on the wing, with Darcy Graham once again named at fullback.
Centre pairing Dean and Johnstone return to the starting line-up after missing the last two games through injury, while stand-off Hickey – who makes his first start since January – is partnered by Henry Pyrgos at half-back.
An unchanged front-row sees captain Stuart McInally pack down alongside props Pierre Schoeman and WP Nel, with club centurions Ben Toolis and Grant Gilchrist named in the second-row.
The inclusion of Barclay at blindside flanker is the only alteration to the back-row as Scotland star Watson and Fijian international No.8 Viliame Mata complete the pack.
Edinburgh team to face Glasgow Warriors at Scotstoun in the Guinness PRO14 on Saturday 27 April (kick-off 7.35pm) – live on Premier Sports
15. Darcy Graham (23)
14. Dougie Fife (123)
13. James Johnstone (40)
12. Chris Dean (85)
11. Duhan van der Merwe (40)
10. Simon Hickey (18)
9. Henry Pyrgos (23)
1. Pierre Schoeman (22)
2. Stuart McInally (136) CAPTAIN
3. WP Nel (133)
4. Ben Toolis (109)
5. Grant Gilchrist (136)
6. John Barclay (4)
7. Hamish Watson (99)
8. Viliame Mata (59)
Replacements: 16. Ross Ford (198); 17. Rory Sutherland (74). 18. Simon Berghan (66); 19. Callum Hunter-Hill (17); 20. Magnus Bradbury (64); 21. Charlie Shiel (5); 22. Jason Baggott (1); 23. Mark Bennett (19)
Unavailable due to injury: Allan Dell; Cameron Fenton; David Cherry; Lewis Carmichael; Jamie Ritchie; Jaco van der Walt; Damien Hoyland; Blair Kinghorn