After missing out on the Autumn Test matches through injury, Exeter lock Gray starts for the first time since March 2021 when he played against Ireland.
He is joined in the second row by Edinburgh's Grant Gilchrist, who will be one appearance away from reaching 50 caps after stepping out against England.
Elsewhere in the forwards pack, Worcester prop Rory Sutherland is named after playing in all of last year's Six Nations matches. He is joined in the front row by Glasgow pair, hooker George Turner and prop Zander Fagerson.
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Edinburgh duo Jamie Ritchie and Hamish Watson will combine with Matt Fagerson from Glasgow in the back row.
Racing 92's Finn Russell and Glasgow's Ali Price will partner each other at nine and 10 respectively for the fourth-consecutive game, while Worcester's Duhan Van Der Merwe starts on the wing.
Darcy Graham will be on the opposite flank following some impressive form with Edinburgh.
Gloucester's Chris Harris and Glasgow's Sam Johnson are set to combine in the centre once again, with captain Stuart Hogg starting at full-back in his ninth Calcutta Cup match.
On the bench, London Irish scrum-half Ben White will have the opportunity to make his Scotland debut, with Edinburgh's Blair Kinghorn and Glasgow's Sione Tuipulotu other options in the backs.
Magnus Bradbury is also among the replacements and could make his first appearance for Scotland since 2020, while Sam Skinner, WP Nel, Pierre Schoeman and Stuart McInally are also on the bench.