Weir starts because of injuries sustained by Finn Russell and Adam Hastings in the course of the win over Wales in Llanelli 11 days ago.
That was their fourth straight victory, bringing down the curtain on a strong Six Nations campaign.
Both fly-halves are out for the foreseeable future, so coach Gregor Townsend will hope Weir’s strong form for Worcester translates to the international stage.
There is also a first start for South African-born wing Duhan van der Merwe in place of the benched Blair Kinghorn, while Sam Johnson returns at inside centre forJames Lang.
The final change is in the forwards, where Stuart McInally, who scored against Wales, comes in for the injured Fraser Brown.
The bench shows considerable change from the Wales win, with Exeter pair Sam Skinner and Sam Hidalgo-Clyne included. Scrum-half Hidalgo-Clyne has not played for Scotland since 2018.
“While we gained confidence from the win over Wales, we have been working hard to improve in all areas of our game, and we believe that there is a lot more to come from this group of players,” said Townsend.
“The energy has been great at training and we are seeing real competition for places throughout our squad.”
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