Joel Tomkins will make his England debut against Australia at Twickenham on Saturday just two years after switching codes from rugby league.
The outside centre has been given the chance to impress by head coach Stuart Lancaster, with Gloucester's Billy Twelvetrees set to partner him at inside centre.
Tomkins' Saracens team-mate Billy Vunipola and London Irish wing Marland Yarde will make their Twickenham debuts after winning their first international caps in Argentina earlier this year.
Lee Dickson, who started both Tests against the Pumas, beats off competition from Ben Youngs and Danny Care to win his 10th cap at scrum-half, with Owen Farrell confirmed as his half-back colleague.
Dan Cole, Ben Youngs and his brother Tom also return to the matchday squad for the opening QBE autumn international.
Lancaster declared himself thrilled to be able to blood some exciting new players against the Wallabies and backed Tomkins to impress.
Grasp his chance
"I'm delighted for Joel. He has had a great week's training and is ready for his chance," said Lancaster.
"He has played in many high-profile games in his career so far and has a great temperament for the big occasion. Joel's big-game temperament will shine through on the weekend."
Lancaster said opting to start Dixon instead of the more experienced Youngs was based purely on current form.
"Form has always been the over-riding factor for me, but Lee also has a lot of credit in the bank," Lancaster added.
"At the start of the season in a competitive position he's the one who's really shined. It's a competitive position but on form alone he deserves it.
"To be picked for this England team you have to be playing well and that's reflected in the selection."
Lancaster urged Courtney Lawes to take the initiative at the line-out after Geoff Parling was ruled out of the autumn opener.
"You lose a lot of experience with Geoff and I'm disappointed that he's injured," he said. "But it's time for Courtney to come in and show his leadership in the line out
"Dave Attwood is match fit and adds ballast and size to our bench.
"Billy Vunipola and Maland Yarde made a big impression in Argentina and it's going to be a special occasion for them to run out at Twickenham in front of 82,000 passionate supporters for the first time.
"It's eight months since we played at our home (in the Six Nations against Italy) and we are looking forward to getting back there for the QBE Internationals and what is a very important series for us two years out from the World Cup."
England: Brown, Ashton, Tomkins, Twelvetrees, Yarde, Farrell, Dickson; M Vunipola, T Youngs, Cole, Launchbury, Lawes, Wood, Robshaw (capt), B Vunipola
Replacements: Hartley, Marler, Wilson, Morgan, B Youngs, Flood, Foden
Watch England take on Australia this Saturday. Coverage starts on Sky 3D and Sky Sports 2 HD from 1:30pm.
Saturday's result at Twickenham?
England by 1-10 points
Australia by 1-10 points
England by 11-20 points
Australia by 11-20 points
England by 21+ points
Australia by 21+ points