Saints hooker Dylan Hartley will captain England against Australia in the first match of the three-Test series in Brisbane on Saturday (ko 11am).
Hartley is joined in the starting XV by Saints team-mate Luther Burrell, while Courtney Lawes and Paul Hill are named on the bench.
There is no place in the matchday 23 for the fifth Saints player in the squad, Teimana Harrison.
“We have picked a side to win in Brisbane,” said England head coach Eddie Jones.
“As always selection was tight and naturally players are disappointed, but we’ve gone with a 23 that has a good mix of experience and youth.
“We aim to win every Test match we play and I am pleased with our preparation since we landed in Australia.
“The group have acclimatised well, trained hard and there’s a buzz around the camp.”
England have never won a Test series in Australia and Jones urged his side to get the southern hemisphere tour off to a winning start and “create history”.
“If you look at England’s record in Australia it’s pretty ordinary,” he said.
“We’ve only ever won three games in Australia so it’s a great opportunity to put down a marker and create history.
“It’s important we get off to a positive start and we’ll arrive in Brisbane ready to play physical and aggressive rugby.
“It’ll be a great challenge for us and one we’re looking forward to meeting head on
“We’re excited to be playing against a strong Australian team in their backyard.
“The Wallabies are ranked second in the world and have the World Rugby coach of the year, so that’s why they start as favourites. There’s a lot of expectation on them to win the series convincingly.
“We have a young squad with an average age of 24 so we are still developing and improving. It’ll be a great challenge for us and one we’re looking forward to meeting head on.”
England team to face Australia: Mike Brown; Anthony Watson, Jonathan Joseph, Luther Burrell, Marland Yarde; Owen Farrell, Ben Youngs; Mako Vunipola, Dylan Hartley, Dan Cole, Maro Itoje, George Kruis, Chris Robshaw, James Haskell, Billy Vunipola
Replacements: Luke Cowan-Dickie, Matt Mullan, Paul Hill, Joe Launchbury, Courtney Lawes, Danny Care, George Ford, Jack Nowell