George Ford and Owen Farrell will pair up from the start for the first time in 14 months when England host Ireland at Twickenham on Saturday.
Ford continues at fly-half with captain Farrell starting at inside centre and lining up alongside Manu Tuilagi in midfield.
Former age-group international pairing Ford and Farrell last started a Test at 10 and 12 when England lost 23-12 to South Africa in Bloemfontein on June 16, 2018.
Harlequins prop Joe Marler will make his first Test start since coming out of retirement and winning a place in boss Eddie Jones' 31-man World Cup squad.
Tom Curry, Sam Underhill and Mark Wilson have all been passed fit to take on the Irish following injury scares earlier in the week.
"This weekend we will be looking to gain more game fitness and testing different sorts of game strategies," said Jones.
"We have a specific way of how we want to play and the focus is very much on ourselves."
England boss Jones lamented his side's lack of line breaks in last weekend's 13-6 defeat in Wales and challenged his midfield to pass more on Saturday.
Explaining the decision to pair up Ford and Farrell in midfield again, Jones said: "We're just trying a different strategic approach to the game.
"It's about finding out what sort of tactical approaches we can employ and use in Japan, because we're going to need a few.
"We want to see a passing game.
"We played a quite tight game against Wales. Last week there were zero line breaks.
"So we feel like this game we probably need to pass a bit more, and with George at 10 and Owen at 12 we think we can do that."
Jones also hopes gritty flankers Curry and Underhill come through England's final few training sessions unscathed, so the duo can finally pair up in the same back row this weekend.
"They've still got to get through another training session," said Jones.
"They are like the kamikaze kids those two.
"Playing two guys who are pretty good at the breakdown might give us an advantage in that area."
Jones insisted Ben Te'o's decision to sign for Toulon will make no difference to his standby list for the World Cup.
The former Worcester centre, who was left out of Jones' 31-man squad, signed a deal with the French club on Wednesday to rule himself out of future England selections.
"Everyone makes a choice, Ben's made his choice," said Jones. "So we wish him all the best and we just get on with it.
"We got some word that was about to happen. Everyone makes their choice, we were happy for him to make his choice."
Asked if Te'o's decision caused a standby list rethink, Jones said: "Not really, no. We've got that in place."
— England Rugby (@EnglandRugby) August 22, 2019
England team to play Ireland
Forwards: 1 Joe Marler (Harlequins), 2 Jamie George (Saracens), 3 Kyle Sinckler (Harlequins), 4 Maro Itoje (Saracens), 5 George Kruis (Saracens), 6 Tom Curry (Sale Sharks), 7 Sam Underhill (Bath Rugby), 8 Billy Vunipola (Saracens)
Backs: 9 Ben Youngs (Leicester Tigers) , 10 George Ford (Leicester Tigers) , 11 Jonny May (Leicester Tigers), 12 Owen Farrell (CAPTAIN, Saracens), 13 Manu Tuilagi (Leicester Tigers), 14 Joe Cokanasiga (Bath Rugby), 15 Elliot Daly (Saracens)
Replacements: 16 Luke Cowan-Dickie (Exeter Chiefs), 17 Mako Vunipola (Saracens), 18 Dan Cole (Leicester Tigers), 19 Courtney Lawes (Northampton Saints), 20 Mark Wilson (Newcastle Falcons/Sale Sharks), 21 Willi Heinz (Gloucester Rugby), 22 Piers Francis (Northampton Saints), 23 Jonathan Joseph (Bath Rugby)