Scotland welcome back fly-half Finn Russell into the team, while Bath centre Cameron Redpath makes his debut in the Calcutta Cup clash on Saturday.
Russell missed the Autumn Nations Cup after sustaining an injury against Wales in the Six Nations but he returns and will have the talents of youngster Redpath outside him this weekend.
Among the five changes to the starting line-up from the final 2020 Six Nations match against Wales in Llanelli in October a new pair of wings will feature as Sean Maitland and Duhan van der Merwe both start.
Issues at hooker
In the pack, Matt Fagerson is selected at number eight and George Turner starts at hooker to make his Six Nations competition debut with Fraser Brown and Stuart McInally injured.
Experienced scrum-half Ali Price will partner Russell in the half-backs, with Chris Harris alongside Redpath in the centres.
Up front Rory Sutherland and Zander Fagerson will pack down with hooker Turner in the front-row.
Scott Cummings and Jonny Gray continue their second-row partnership, with Hamish Watson and Jamie Ritchie completing the pack.
Edinburgh hooker David Cherry will make his Scotland debut if called up from the replacements. WP Nel and Oli Kebble are the other front-row cover, alongside fellow forwards Richie Gray and Gary Graham. Scott Steele, Jaco van der Walt and Huw Jones complete the matchday 23.
Head coach Gregor Townsend said: “This most historic of fixtures against England is a great start to the 2021 Guinness Six Nations and a challenge we will fully embrace with the objective of playing to our potential and ultimately lifting our supporters in these difficult times.
That out-the-back flick from @camredpath 😍
And big @J_cokanasiga back and scoring is a wonderful sight to see 👌
— Premiership Rugby (@premrugby) November 26, 2020
“We learned a lot about ourselves and where the game is going during our Autumn campaign, and we aim to build on this base during the next seven weeks. We are set for a huge challenge against England as we will be facing one of the best teams in the world.
“It’s always a pleasure to welcome a new player into our squad and we are looking forward to Cam Redpath winning his first cap on Saturday. We have been really impressed with Cam’s contributions in the time he has been with us in camp.
“There are a number of experienced players in the backline to help make his transition to Test rugby go as smoothly as possible, and he has the mindset and skillset to thrive at this level.
“The opportunity of competing for the Calcutta Cup against our oldest rivals is something to get Scots around the world excited about.”
Scotland: 15 Stuart Hogg (c), 14 Sean Maitland, 13 Chris Harris, 12 Cameron Redpath, 11 Duhan van der Merwe, 10 Finn Russell, 9 Ali Price, 8 Matt Fagerson, 7 Hamish Watson, 6 Jamie Ritchie, 5 Jonny Gray, 4 Scott Cummings, 3 Zander Fagerson, 2 George Turner, 1 Rory Sutherland
Replacements: 16 David Cherry, 17 Oli Kebble, 18 WP Nel, 19 Richie Gray, 20 Gary Graham, 21 Scott Steele, 22 Jaco van der Walt, 23 Huw Jones
Date: Saturday, February 6
Kick-off: 16:45 GMT
Referee: Andrew Brace (Ireland)
Assistant Referees: Pascal Gauzere (France), Mathieu Raynal (France)
TMO: Joy Neville (Ireland)