The 31-year-old is the only Scot to have been nominated for the IRB's player-of-the-year award, in 2008, and retires with 85 caps to his name, 14 as captain.
New Scotland coach Scott Johnson will now be hoping Glasgow Warriors scrum-half Chris Cusiter recovers in time for this year's Six Nations campaign.
Henry Pyrgos - having starred for the Warriors on RaboDirect PRO12 duty this season and played three times this autumn - will also be in the running along with Rory Lawson and Greig Laidlaw.
And it is the likes of 23-year-old Pyrgos that Blair had in mind when making his retirement decision.
"I'm in the very fortunate position of being able to decide myself when my international career ends, for me, that time is now," said Blair, who moved fromEdinburgh to Brive in the summer.
"A place in the squad at the World Cup in 2015 is not a realistic personal target and, with that in mind, it's right for Scottish rugby and the Scotland team, that other players gain experience in a pivotal position.
"There's no doubt that moving our family to France has played a part in my decision. Our son Rory is now at school here and we have an 11-week-old daughter, Lucy, who was born in Brive.
"However, it's a combination of reasons that's led to my standing down from international rugby, not just one factor.
"I have enjoyed immensely representing my country for more than ten years and will miss that exhilarating feeling of running out to a capacity crowd with the whole country behind you.
"The noise when leading the team out for the first time as captain at Murrayfield against England in 2008, when we won 15-9, still makes the hair on the back of my neck stand up when I think about it.
"I want to thank everyone - my family, the Scotland management teams past and present, my team mates and our supporters - for their enormous contribution to my international career. I have been very fortunate to have these people around me."