Fin Smith will start at fly-half, Marcus Smith at fullback, and regular captain Maro Itoje will be on the bench, as England head coach Steve Borthwick once again shuffles his combinations.
Chandler Cunningham-South, who can play at flanker and second row, will make his Test debut at number eight. Borthwick is keen to give other players opportunities in this position after Tom Willis's move to France at the end of the season ruled him out of international contention.
Tom Roebuck has been ruled out after aggravating an ankle injury in training on Tuesday, while Tommy Freeman returns on the wing, allowing Ollie Lawrence to make his international comeback at centre.
Lawrence suffered an Achilles tendon injury during the Six Nations victory against Italy in March but has recovered quicker than expected following rehabilitation involving a hyperbaric chamber and red light therapy, which he documented on social media.
Northampton's Alex Coles comes into the second row, while Itoje's impact is being saved for the second half. Prop Ellis Genge, who returns to the starting lineup, will captain the side from the outset.
George Ford, who captained England during the successful summer tour of America when both Fin and Marcus Smith were on British and Irish Lions duty, has been left out of the matchday squad entirely.