The 2009 Lion will start the Millennium Stadium encounter with Wales having missed Sunday's opening defeat to France due to religious commitments.
While Murray's return is a huge boost, it is Edinburgh full back Chris Paterson who has stolen the headlines prior to the trip to Cardiff.
Paterson will become the first Scottish player to win 100 international caps when he lines up alongside Murray this weekend.
Having made his 99th appearance in the defeat to France last Sunday, the 31-year-old has been selected in the No15 shirt once more for Saturday's 2pm kick-off.
Paterson will become just the second Celt to reach the magical milestone, following in the footsteps of former Lions skipper and Wales star Gareth Thomas.
A total of nine other players have won a century of international caps, with Australia's George Gregan leading the way with 139 and Lions legend Jason Leonard third on the list with 114.
"Chris has been a fantastic ambassador for the team and it's a tremendous honour for him to win his 100th cap," said Scotland head coach Andy Robinson.
"It's well-deserved and I'm looking forward to seeing him perform at the weekend."
Paterson is joined in the Scotland starting XV by 2009 Lions Ross Ford and Nathan Hines, as well as 2005 tourist Chris Cusiter.
The fine Magners League form of Glasgow Warriors fly-half Dan Parks' has seen him oust Phil Godman from the No10 shirt, while Toulon's Rory Lamont comes in on the left wing, with Sean Lamont of the Scarlets moving to outside centre and Glasgow's Max Evans dropping to the bench.
Scrum-half Mike Blair, a Lion last summer, is included among the replacements having made his comeback from injury with the Scotland A side last week.
Scotland squad to face Wales on Saturday, February 13 at the Millennium Stadium
15 Chris Paterson (Edinburgh)
14 Thom Evans (Glasgow Warriors)
13 Sean Lamont (Scarlets)
12 Graeme Morrison (Glasgow Warriors)
11 Rory Lamont (Toulon)
10 Dan Parks (Glasgow Warriors)
9 Chris Cusiter (Glasgow Warriors)
1 Alasdair Dickinson (Gloucester)
2 Ross Ford (Edinburgh)
3 Euan Murray (Northampton Saints)
4 Nathan Hines (Leinster)
5 Alastair Kellock (Glasgow Warriors)
6 Kelly Brown (Glasgow Warriors)
8 Johnnie Beattie (Glasgow Warriors)
7 John Barclay (Glasgow Warriors)
16 Scott Lawson (Gloucester)
17 Allan Jacobsen (Edinburgh)
18 Richie Gray (Glasgow Warriors)
19 Alan MacDonald (Edinburgh)
20 Mike Blair (Edinburgh)
21 Phil Godman (Edinburgh)
22 Max Evans (Glasgow Warriors)
Bold denotes Lion