Hooker Jamie George will finally make his first start for England after 19 appearances off the bench as coach Eddie Jones on Thursday named a side featuring nine changes to play Samoa at Twickenham on Saturday.
George was first-choice hooker for the British & Irish Lions in New Zealand this year but for the last two years has had to sit behind Dylan Hartley for England.
The captain is on the bench this week, while several other key players have been left out of the squad.
Jones was always expected to experiment for Saturday's match, which should be a straightforward one against a Samoa team struggling for any sort of form.
Scrumhalf Danny Care, who set up two tries and scored a third in a superb late cameo in last week's record win over Australia, gets a rare start, while Alex Lozowski and Henry Slade will form an exciting new centre partnership.
Sam Simmonds will make his first start at number 8 in the absence of the injured Nathan Hughes, with Charlie Ewels in the second row and Mike Brown returning at fullback.
With Owen Farrell again rested, flyhalf George Ford and Chris Robshaw, switched to openside flanker, have been named co-captains as England expect to complete a hat-trick of wins from their November tests.
"This week it is an opportunity for some squad members who haven't been playing to put their best foot forward," Jones said.
"We want to follow up last week's performance against Australia and play better again this week but we are expecting Samoa to be immensely physical and committed."
There is never any doubt about that, but the islanders have shown precious little else over the last few years during a dire run.
Last week they were beaten by Romania to extend their losing streak to eight matches, while they have lost all seven of their previous games against England, the most recent being a 28-9 defeat three years ago.
Samoa was changed by only three from the side which lost its tour opener to Scotland 44-38 at Murrayfield.
Rey Lee-Lo, who played inside centre against Scotland and in the 17-13 loss to Romania last weekend, has been dropped to the reserves for Bristol's Alapati Leiua. Dwayne Polataivao has held on as starting scrumhalf from the Romania game.
England: Mike Brown, Jonny May, Henry Slade, Alex Lozowski, Elliot Daly, George Ford (co-captain), Danny Care; Sam Simmonds, Chris Robshaw (co-captain), Maro Itoje, Charlie Ewels, Joe Launchbury, Dan Cole, Jamie George, Ellis Genge. Reserves: Dylan Hartley, Joe Marler, Harry Williams, Nick Isiekwe, Courtney Lawes, Ben Youngs, Piers Francis, Semesa Rokoduguni.
Samoa: Ah See Tuala, Paul Perez, Kieron Fonotia, Alapati Leiua, David Lemi, Tim Nanai-Williams, Dwayne Polataivao; Jack Lam, TJ Ioane, Piula Fa'asalele, Chris Vui (captain), Josh Tyrell, Donald Brighouse, Motu Matu'u, Jordan Lay. Reserves: Manu Leiataua, James Lay, Hisa Sasagi, Fa'atiga Lemalu, Ofisa Treviranus, Melani Matavao, Rey Lee-Lo, JJ Taulagi.
