Head coach Andy Robinson has responded to the 21-10 defeat by South Africa by starting with Glasgow Warriors scrum-half Pyrgos, who impressed as a replacement for Mike Blair on Saturday at Murrayfield.
Blair, hooker Ross Ford and lock Jim Hamilton have been dropped from the matchday 23 altogether.
Scott Lawson starts in place of former captain Ford, with Alastair Kellock taking Hamilton's place in the second row alongside Richie Gray, who suffered concussion against the Springboks and will continue to be monitored.
Alasdair Strokosch, who was a late withdrawal from the starting XV due to a calf injury, returns in place of John Barclay, while Max Evans starts at outside centre, with Nick De Luca dropping to the bench.
Pyrgos has been promoted after Blair's intercept pass allowed South Africa hooker Adriaan Strauss to score his second try in the loss on Saturday.
The Glasgow number nine made an instant impact, scoring moments after entering the fray.
Rory Lawson returns as replacement scrum-half, having not played since the World Cup loss to Argentina in Wellington, and is joined on the bench by uncapped Inverness-born Bath fly-half Tom Heathcote.
Heathcote was drafted into the squad on Monday following the release of Ruaridh Jackson and is the understudy to Greig Laidlaw at number 10.
Outside Laidlaw sees a new centre combination, with Matt Scott combining with Evans, while the back three of Tim Visser, Sean Lamont and Stuart Hogg remains unchanged.
Alongside Scott Lawson in the front row is Ryan Grant and Euan Murray, with Gray and Kellock behind them and uncapped Edinburgh lock Grant Gilchrist in reserve.
Blindside flanker Strokosch is joined in the back-row by captain Kelly Brown and number eight David Denton, with Barclay a substitute.
The defeat saw Scotland fall to 10th in the world rankings ahead of the December 3 2015 World Cup draw.
Robinson said: "We will not be among the top eight seeds for the 2015 Rugby World Cup draw, so this weekend I'm looking at giving a number of players an opportunity to put their hand up for selection for next year.
"This weekend we have to put together an 80-minute performance and build on the positive parts of our games that we showed in the last 30 minutes against South Africa and the second-half against New Zealand.
"International rugby is about pressure and it's important that you convert your pressure into points and when you are under pressure that you are able to absorb it as opposed to conceding points as cheaply as we have done."