Blair, who was a pre-tour call up for the Lions' summer trip to South Africa, was concussed in Edinburgh's Magners League win over the Ospreys last weekend.
Scrum-half rival and fellow joint-Scotland captain Cusiter, who toured New Zealand with the Lions five years ago, has recovered from a virus to take his place in the starting line up, with Gloucester's Rory Lawson replacing Blair on the bench.
Edinburgh's Nick De Luca is the only personnel change to the starting XV that lost to Italy in Rome last time out.
The 26-year-old is chosen at outside centre for the Calcutta Cup tie at Murrayfield having not started for his country for 16 months since the win over Canada at Pittodrie in November 2008.
De Luca wins his 16th cap after impressing for Edinburgh last weekend.
Glasgow centre Max Evans switches to the left wing, with Ulster's Simon Danielli dropping to the bench.
Gloucester duo Alasdair Strokosch and Alasdair Dickinson join Blair in missing out through injury but Glasgow back row John Barclay has recovered from a knee injury to take his place in the starting line up.
Blair's Edinburgh clubmates Geoff Cross and Alan MacDonald feature on the replacements bench having not been involved against the Italians.
"The team has played some good rugby and we have been creating chances. We just need to take that next step and finish off a game," said Scotland head coach Andy Robinson, a former coach of the England national side and an ex-England international.
Scotland have a total of four Lions in their matchday 22, with Cusiter, Ross Ford and Euan Murray all set to start and Nathan Hines named among the replacements.
15 H Southwell (Stade Francais)
14 S Lamont (Scarlets)
13 N De Luca (Edinburgh)
12 G Morrison (Glasgow)
11 M Evans (Glasgow)
10 D Parks (Glasgow)
9 C Cusiter (Glasgow, captain)
1 A Jacobsen (Edinburgh)
2 R Ford (Edinburgh)
3 E Murray (Northampton)
4 J Hamilton (Edinburgh)
5 A Kellock (Glasgow)
6 K Brown (Glasgow)
7 J Barclay (Glasgow)
8 J Beattie (Glasgow)
16 S Lawson (Gloucester)
17 G Cross (Edinburgh)
18 N Hines (Leinster)
19 A MacDonald (Edinburgh)
20 R Lawson (Gloucester)
21 P Godman (Edinburgh)
22 S Danielli (Ulster)
Bold denotes Lion