The changes see Simon Danielli, Joe Ansbro and Rory Lawson listed in the back division, while Nathan Hines is re-introduced in the blindside flanker berth he occupied against France in the first game of the championship, with Kelly Brown moving to No 8 from the side of the scrum.
It will be Danielli's first start of the championship; Ansbro returns after missing the Ireland game through concussion in a club match; and Lawson is back in the No 9 shirt he wore against the Welsh.
Edinburgh duo Mike Blair and Nick De Luca will be on the bench, where they are joined for the first time in this championship by Gloucester flanker, 28-year-old Alasdair Strokosch, who missed the EMC Autumn Tests on account of a knee injury.
Wing Nikki Walker and No8 Johnnie Beattie are omitted altogether from the team that lost 18-21 to Ireland in Scotland's last outing.
This weekend's game marks 100 years since the first time Scotland visited Twickenham to face England. In total they have played at "Billy Williams' cabbage patch" on 44 occasions and have won on only four of them - the most recent 28 years ago.
Scotland head coach Andy Robinson said:
"The record books show what a special achievement it would be for the Scotland team to win on Sunday. That is our intention and we firmly believe that if we can deliver a sustained, intelligent and ruthless performance then we can achieve our first win of this season's championship.
"England have played some good rugby in this championship but Sunday is about our performance. Simon Danielli and Rory Lawson have both been playing well for their clubs and Joe Ansbro was unfortunate to miss the game against Ireland through injury, while Nathan Hines' experience will be an asset for us in our back-row."
Paterson (Edinburgh); Danielli (Ulster), Ansbro (Northampton), S Lamont Scarlets), M Evans (Glasgow Warriors); Jackson (Glasgow Warriors), R Lawson (Gloucester); Jacobsen (Edinburgh), Ford (Edinburgh), Low (Glasgow Warriors), Gray (Glasgow Warriors), Kellock (Glasgow Warriors, captain), Hines (Leinster), Barclay (Glasgow Warriors), Brown (Saracens).
S Lawson (Gloucester), Cross (Edinburgh), Vernon (Glasgow Warriors), Strokosch (Gloucester), Blair (Edinburgh), Parks (Cardiff Blues), De Luca (Edinburgh).