Care, who will be in direct opposition to Scotland captain Greig Laidlaw, has been preferred ahead of long-term rival Ben Youngs in the No 9 jersey for the trip to Edinburgh, while Marler has been given the nod ahead of Mako Vunipola.
Back row Jack Clifford, prop Paul Hill and centre Ollie Devoto are set to make their international debuts off the bench at Murrayfield.
Lock Courtney Lawes is included among the replacements after passing a fitness test on his hamstring injury.
“There were some tight calls on selection, but we have picked a match-day squad with a blend of experience and youth,” England head coach Eddie Jones said.
Northampton hooker Dylan Hartley leads a starting XV containing 512 caps – but no debutants – as England seek to retain the Calcutta Cup, which they have held since 2009.
Jones has announced that Owen Farrell – selected at centre – No 8 Billy Vunipola and full-back Mike Brown have been appointed vice-captains to support Hartley.
Chris Robshaw is moved across the back row to blindside flanker with James Haskell taking his previous position at openside.
Jones’ solution to England’s perennial midfield conundrum is to field George Ford at fly-half and Farrell at inside centre in their second Test start together.
The other options at 12 – Henry Slade and Manu Tuilagi – are to miss all or a substantial chunk of the Six Nations though injury.
“The boys have worked hard since coming into camp to understand how I want the team to play going forward,” Jones said.
“We have prepared well and I am pleased with the progress the group has made in the short time we’ve had together.
“We are indebted to the work Stuart Lancaster has done over last four years. I have inherited a talented and highly motivated group of players.
“We are confident we can go to Edinburgh and win, but we’re in no doubt it will be a huge challenge.
“Playing at Murrayfield in front of a passionate Scottish crowd will be a real test for this team but one I know we can rise to.”
Lancaster, Jones’ predecessor, gave three players debuts in his first match in charge - also at Murrayfield - and capped another four off the bench.
Scotland are due to name their team later on Thursday.