The Northampton Saints back row man, who was born in Zimbabwe and learned his rugby in Australia, takes over from John Barclay after coming on as a replacement in six Tests this season.
Scottish coach Frank Hadden, under pressure to deliver a second championship win this season, has made only one change to the starting line-up for the trip to Twickenham at the Cal,cutta Cup showdown.
Now 31, Gray gets the nod over Barclay in the team and Glasgow's Kelly Brown takes his place among the replacements.
"Scott has been knocking on the door for some time now and deserves this opportunity, while we've gone for Kelly on the bench for the coverage that he provides," said Scottish coach Frank Hadden..
"We're looking forward to going to Twickenham and seeking back to back Calcutta Cup wins for the first time since 1984."
Scotland: Chris Paterson (Edinburgh); Simon Danielli (Ulster), Max Evans (Glasgow Warriors), Graeme Morrison (Glasgow Warriors), Thom Evans (Glasgow Warriors); Phil Godman (Edinburgh), Mike Blair (Edinburgh, captain);
Alasdair Dickinson (Gloucester), Ross Ford (Edinburgh), Euan Murray (Northampton Saints), Jason White (Sale Sharks), Jim Hamilton (Edinburgh), Alasdair Strokosch (Gloucester), Scott Gray (Northampton Saints), Simon Taylor (Stade Francais).
Replacements: Dougie Hall (Glasgow Warriors), Moray Low (Glasgow Warriors), Nathan Hines (Perpignan), Kelly Brown (Glasgow Warriors), Chris Cusiter (Perpignan), Nick De Luca (Edinburgh), Hugo Southwell (Edinburgh).