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Centre Lawrence replaces Fraser Dingwall - a try scorer in England's 16-14 win over Wales in Round 2 - while 37-year-old scrum-half Care comes in start in place of the injured Alex Mitchell (knee) for his 99th Test cap.
Props Genge and Cole shift from the bench to start, with Marler taking a place as a replacement.
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Elsewhere, George Furbank replaces Freddie Steward at 15, with wings Tommy Freeman and Elliot Daly to form the back-three, while Henry Slade partners Lawrence in midfield.
George Ford starts again at fly-half, while skipper and hooker Jamie George and tighthead Dan Cole combine with Genge in the front row.
Maro Itoje and Ollie Chessum partner one another in the second row once more, while the back row is unchanged too in the shape of blindside Ethan Roots, openside Sam Underhill and No 8 Ben Earl.
Among the replacements, Leicester lock George Martin comes into the squad, replacing Alex Coles, while Bath scrum-half Ben Spencer is also brought in.
Hooker Theo Dan, tighthead Will Stuart, back row Chandler Cunningham-South, fly-half Fin Smith and wing Immanuel Feyi-Waboso complete the squad.
Head coach Steve Borthwick said: "We're pleased with the start we've made to our Six Nations campaign but know that a difficult test awaits us in Edinburgh against an in-form Scotland team"
"The atmosphere is always special for any Calcutta Cup match and I'm sure this weekend's game at Murrayfield will be no different.
England: 15 George Furbank, 14 Tommy Freeman, 13 Henry Slade, 12 Ollie Lawrence, 11 Elliot Daly, 10 George Ford, 9 Danny Care; 1 Ellis Genge, 2 Jamie George (c), 3 Dan Cole, 4 Maro Itoje, 5 Ollie Chessum, 6 Ethan Roots, 7 Sam Underhill, 8 Ben Earl.
Replacements: 16 Theo Dan, 17 Joe Marler, 18 Will Stuart, 19 George Martin, 20 Chandler Cunningham-South, 21 Ben Spencer, 22 Fin Smith, 23 Immanuel Feyi-Waboso.
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