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 trip to the Millennium Stadium.
Paterson will become just the second Celt to reach the magical milestone, following in the footsteps of former Wales skipper and current Cardiff Blues 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.
"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 Glasgow Warriors fly-half Dan Parks, whose fine Magners League form has seen him oust Phil Godman from the No10 shirt.
Tight-head prop Euan Murray returns to the side after he missed Sunday's opening Six Nations tie through religious commitments, 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.
Edinburgh scrum-half Mike Blair is included among the replacements having made his comeback from injury with the Scotland A side last week.
There are just four non-Magners League players in the matchday 22, with Glasgow providing 10 squad members, Edinburgh six and the Scarlets and Leinster providing one apiece.
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)
Replacements
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)
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