Uncapped pair Guy Porter and Tommy Freeman will make their England debuts after they were named in Eddie Jones' starting XV for the second Test against Australia.
The tourists will also hand a first start to Tigers scrum-half Jack van Poortvliet as they ring the chances for the must-win encounter against the Wallabies in Brisbane on Saturday.
Despite a man advantage after Darcy Swain's first-half dismissal in Perth, Jones' side slid to a 30-28 loss at Optus Stadium last weekend in their first encounter.
That has prompted a flurry of changes from the Australian, in what some may see as a risky gamble as he seeks to level the three-match series in what could be humid winter conditions in Queensland.
Leicester title-winning centre Porter will make his bow, while Freeman – who featured last month in an uncapped game against the Barbarians – will make his international debut proper.
Sam Underhill moves up to take the place of Tom Curry, who has been ruled out of the rest of the tour through concussion, while Owen Farrell has been retained at inside centre.
"We have decided to make changes in our backline, they were tough calls, but we feel they will strengthen the team," Jones said. "There are opportunities to attack against Australia which we can take."
Australia meanwhile have been forced into a slate of swaps, through Swain's suspension and Tom Banks' injury, with Matt Philip in for the former and Jordan Petaia moved to full-back to cover the latter's absence.
In a significant boost, prop Taniela Tupou is back, and makes a like-for-like change with the injured Allan Ala'alatoa.
Australia team: Petaia, Wright, Paisami, Kerevi, Koroibete, Lolesio, White; Bell, Porecki, Tupou, Philip, Neville, Leota, Hooper, Valetini.
Replacements: Fainga'a, Sio, Slipper, Frost, Samu, Gordon, O'Connor, Perese.
England team: Steward, Nowell, Porter, Farrell, Freeman, Smith, Van Poortvliet; Genge, George, Stuart, Itoje, Hill, Lawes, Underhill, B Vunipola.
Replacements: Cowan-Dickie, M Vunipola, Heyes, Chessum, Ludlam, Willis, Care, Arundell.