Hamilton made his first start, and his third appearance in international colours, during the defeat by England last Saturday and coach Frank Hadden has kept faith with the 24-year-old for this weekend.
He does, though, have a new partner in the second row with Scott Murray returning for his 81st cap in place of Alastair Kellock. Nathan Hines comes on to the bench, where Murray started last Saturday's match.
Hadden's other changes see Edinburgh Rugby duo Rob Dewey and Phil Godman make their first starts of the Championship with Andrew Henderson and Dan Parks stepping down.
Back rower Simon Taylor will become the 21st Scot to reach the landmark of 50 caps on Saturday.
Scotland team (v Wales, on Saturday, kick-off 3.30pm)
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 Phil Godman (Edinburgh Rugby)
9 Chris Cusiter (Border Reivers)
1 Gavin Kerr (Border Reivers)
2 Dougie Hall (Edinburgh Rugby)
3 Euan Murray (Glasgow Warriors)
4 James Hamilton (Leicester Tigers)
5 Scott Murray (Edinburgh Rugby)
6 Simon Taylor (Edinburgh Rugby)
8 David Callam (Edinburgh Rugby)
7 Kelly Brown (Border Reivers)
16 Ross Ford (Border Reivers)
17 Allan Jacobsen (Edinburgh Rugby)
18 Nathan Hines (Perpignan)
19 Allister Hogg (Edinburgh Rugby)
20 Rory Lawson (Gloucester)
21 Simon Webster (Edinburgh Rugby)
22 Nikki Walker (Neath Swansea Ospreys)