Hamilton started the tournament's opening two fixtures against England and Wales and was on the bench for last weekend's defeat to Italy.
Dan Parks is restored to stand off as the only change in the Scotland starting XV. Parks will be winning his 29th cap and replaces Phil Godman. On the bench Rory Lamont returns instead of Nikki Walker.
Scotland head coach Frank Hadden said: "We've chosen Dan at stand-off as we feel he has the right qualities for this game. Rory Lamont has been preferred on the bench as he provides greater cover."
He went on: "We firmly believe we are capable of upsetting the form book and beating a very good Irish side. Nobody would enjoy that scenario more than Scott Murray who will set a new Scottish cap record on Saturday."
Scotland vs Ireland, Murrayfield, Saturday March 10, kick-off 1.30pm
15 Hugo Southwell (Edinburgh Rugby)
14 Sean Lamont (Northampton Saints)
13 Marcus Di Rollo (Edinburgh Rugby)
12 Rob Dewey (Edinburgh Rugby)
11 Chris Paterson (Edinburgh Rugby) (captain)
10 Dan Parks (Glasgow Warriors)
9 Chris Cusiter (Border Reivers)
1 Gavin Kerr (Border Reivers)
2 Dougie Hall (Edinburgh Rugby)
3 Euan Murray (Glasgow Warriors)
4 Nathan Hines (Perpignan)
5 Scott Murray (Edinburgh Rugby)
6 Simon Taylor (Edinburgh Rugby)
7 Kelly Brown (Border Reivers)
8 David Callam (Edinburgh Rugby)
16 Ross Ford (Border Reivers)
17 Allan Jacobsen (Edinburgh Rugby)
18 Jim Hamilton (Leicester Tigers)
19 Allister Hogg (Edinburgh Rugby)
20 Rory Lawson (Gloucester)
21 Andrew Henderson (Glasgow Warriors)
22 Rory Lamont (Glasgow Warriors)