On the Scots' replacements bench, meanwhile, there are three changes with Euan Murray, Ruaridh Jackson and Max Evans coming in for Ed Kalman, Duncan Weir and De Luca respectively.
Scotland head coach Andy Robinson said: "We did many good things in the game against France but we need to be better, especially in our accuracy and execution at breakdown, in order to beat Ireland.
"If we do the basic things well and are ruthless in contact then we can put ourselves in a position to defeat a very good Ireland team."
Robinson is asking De Luca to replicate the form he showed against France by handing him the starting berth, while he also welcomes back Jackson as reserve out-half.
"Ruaridh has worked hard and done well in his games with Glasgow," he added.
"He had a tough time with injury following the Rugby World Cup but he has the strength of character required in international rugby.
"We are also delighted to see Max and Euan back in the squad and look forward to their contribution this weekend."
SCOTLAND Team & Replacements (v Ireland, 2012 RBS 6 Nations Championship, Aviva Stadium, Saturday, March 10, kick-off 5pm):
15. Stuart Hogg (Glasgow Warriors)
14. Lee Jones (Edinburgh)
13. Nick De Luca (Edinburgh)
12. Graeme Morrison (Glasgow Warriors)
10. Greig Laidlaw (Edinburgh)
9. Mike Blair (Edinburgh)
1. Allan Jacobsen (Edinburgh)
2. Ross Ford (Edinburgh) (capt)
3. Geoff Cross (Edinburgh)
4. Richie Gray (Glasgow Warriors)
5. Jim Hamilton (Gloucester)
6. John Barclay (Glasgow Warriors)
7. Ross Rennie (Edinburgh)
8. David Denton (Edinburgh)
16. Scott Lawson (Gloucester)
17. Euan Murray (Newcastle Falcons)
18. Alastair Kellock (Glasgow Warriors)
19. Richie Vernon (Sale Sharks)
20. Chris Cusiter (Glasgow Warriors)
21. Ruaridh Jackson (Glasgow Warriors)
22. Max Evans (Castres Olympique)