The South African-born fly-half qualified on residency grounds last month and has been picked to start in Dublin in the Autumn Nations Cup third-place play-off.
Duncan Weir drops out of the match-day 23.
Van der Walt is one of six changes from the side which lost to France at BT Murrayfield.
Duncan Taylor has been selected at inside centre in place of Sam Johnson and will make his first Scotland start since the defeat of Russia at last year’s Rugby World Cup.
Edinburgh winger Darcy Graham regains his place on the wing ahead of the injured Blair Kinghorn.
In the front row, props Rory Sutherland and Zander Fagerson return to the XV.
Blade Thomson is also back, but at blindside flanker, with Jamie Ritchie moving to the openside.
Glasgow back Huw Jones and London Irish flanker Blair Cowan are set to make their first appearances of the autumn campaign from the bench.
And winger Sean Maitland is also among the replacements and will win his 50th cap should he be called upon.
Scotland team (v Ireland, Aviva Stadium, Dublin, Saturday, 2.15pm)
15. Stuart Hogg (Exeter Chiefs) captain
14. Darcy Graham (Edinburgh)
13. Chris Harris (Gloucester)
12. Duncan Taylor (Saracens)
11. Duhan van der Merwe (Edinburgh)
10. Jaco van der Walt (Edinburgh)
9. Ali Price (Glasgow Warriors)
1. Rory Sutherland (Edinburgh)
2. Fraser Brown (Glasgow Warriors)
3. Zander Fagerson (Glasgow Warriors)
4. Scott Cummings (Glasgow Warriors)
5. Jonny Gray (Exeter Chiefs)
6. Blade Thomson (Scarlets)
7. Jamie Ritchie (Edinburgh)
8. Matt Fagerson (Glasgow Warriors)
16. Stuart McInally (Edinburgh)
17. Oli Kebble (Glasgow Warriors)
18. Willem Nel (Edinburgh)
19. Sam Skinner (Exeter Chiefs)
20. Blair Cowan (London Irish)
21. Sam Hidalgo-Clyne (Exeter Chiefs)
22. Huw Jones (Glasgow Warriors)
23. Sean Maitland (Saracens)
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