Fellow ex-Hawick player Rory Sutherland drops to the bench, however, after starting against England last Saturday.
The 29-year-old is joined there by Cameron Redpath, son of Galashiels-born former Scotland captain Bryan Redpath, and ex-Melrose and Southern Knights openside flanker Rory Darge.
Head coach Gregor Townsend has named second-row Grant Gilchrist, making his 50th appearance for the Scots, as vice-captain for Saturday’s game at Cardiff's Principality Stadium, kicking off at 2.15pm.
Exactly a decade on from making his Scotland debut against the Welsh in Cardiff, Hogg, 29, will pick up his 90th cap for his country in the very same stadium.
That will leave him just 20 appearances away from matching the current record of 110 held by Kelso’s Ross Ford and 19 behind second-placed Chris Paterson’s 109.
His Exeter Chiefs team-mate Jonny Gray will partner Gilchrist after returning to the Scotland line-up for last weekend’s 20-17 Calcutta Cup victory in Edinburgh.
Fellow Exeter player Sam Skinner takes Jamie Ritchie’s place in one of five changes to last weekend’s starting line-up, Ritchie having been ruled out for the rest of the championship by injury.
Hamish Watson continues in the back row, with No 8 Matt Fagerson also starting.
There are three changes in the front row, with Pierre Schoeman and Willem Nel starting alongside hooker Stuart McInally.
Ali Price and Finn Russell continue their partnership at No 9 and No 10 respectively.
There is only one change in the back line, with Sione Tuipulotu coming in at inside centre, playing alongside Chris Harris.
Worcester Warriors winger Duhan van der Merwe starts too, with Edinburgh’s Graham, 24, lining up on the other wing for his 24th cap.
Joining Sutherland, Bath’s Redpath and Glasgow Warriors’ Darge among the replacements are George Turner, Zander Fagerson, Magnus Bradbury, Ben White and Blair Kinghorn.
Sutherland is currently on 17 caps, with Redpath, 22, on one and Darge, 21, yet to make his debut.
Ex-Gala star Townsend, 48, said: “We only play five games in this championship so you’ve got to make sure you take your opportunities.
“Last week has set us up now for an even bigger game this weekend in terms of where we could finish in the championship.
“All the positive feelings after last week’s result would disappear if we don’t get a win this weekend.
“We know we’re going to have to deliver a better performance this week to get a victory.”
Scotland were edged out 25-24 by Wales in last year’s Six Nations but beat them 14-10 in Llanelli the year before.
They haven’t won in Cardiff since 2002, however, prevailing 27-22 that time round, thanks to two tries by Gordon Bulloch, four penalties and a conversion by Brendan Laney and a penalty by Duncan Hodge.