Alex Mitchell will start at scrum-half for England against Ireland with Marcus Smith set to make his first appearance in this year's Six Nations having been named on the bench.
Fly-half Smith has not featured for England since the World Cup due to a calf injury, while Mitchell missed out against Scotland after suffering a knee injury against Wales.
The changes mean Danny Care drops to the bench, from where he hopes to be brought on for his 100th Test appearance.
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Care made his debut for England in 2008 against New Zealand at the age of 21 and could become England's sixth Test centurion.
The other changes from head coach Steve Borthwick see George Martin come into the pack, moving Ollie Chessum from lock to flanker, and Immanuel Feyi-Waboso makes his first start on the wing, meaning Elliot Daly also drops to the bench.
Elsewhere, an unchanged front row has captain Jamie George joined at hooker alongside vice-captain Ellis Genge on the loosehead and Dan Cole at tighthead.
In the second row, vice-captain Maro Itoje is partnered with Martin on his first start this tournament, while the back row sees Chessum alongside Sam Underhill on the openside and Ben Earl at No 8.
George Ford continues at 10 alongside Mitchell, while Ollie Lawrence and Henry Slade continue their partnership in the centres.
With Feyi-Waboso on the right wing, Tommy Freeman moves to the left wing, George Furbank at full-back once again.
The midfield pairing of Ollie Lawrence at inside centre and Henry Slade at 13 remains the same.
In the back three, Feyi-Waboso is named on the right wing to win his third England cap and his first start of the tournament. Tommy Freeman moves to the left wing and George Furbank is selected at full-back.
Alongside Care, Daly, and Smith the rest of the bench is made up by Theo Dan, Joe Marler, Will Stuart, Chandler Cunningham-South, and Alex Dombrandt.
"As always, we've selected what we think is our strongest 23 to leave us best-placed to win the game," said Borthwick.
"Ireland are without doubt currently one of the best teams in the world, and we'll have to be at our very best against them on Saturday.
"We've prepared well for what will be another classic Six Nations game at Twickenham.
"I'd like to pay special tribute to Danny Care who will win his 100th cap at Twickenham on Saturday.
"Danny has been a tremendous servant to English rugby and reaching this milestone is an incredible achievement.
"He's a wonderful player and someone who always puts the team first. I'm sure Saturday will be an emotional and memorable day for Danny and his family, and the team couldn't be prouder of his accomplishment."
England team to face Ireland
England XI: 15. George Furbank, 14. Immanuel Feyi-Waboso, 13. Henry Slade, 12. Ollie Lawrence, 11. Tommy Freeman, 10. George Ford, 9. Alex Mitchell, 1. Ellis Genge, 2. Jamie George, 3. Dan Cole, 4. Maro Itoje, 5. George Martin, 6. Ollie Chessum, 7. Sam Underhill, 8. Ben Earl
Replacements: 16. Theo Dan, 17. Joe Marler, 18. Will Stuart, 19. Chandler Cunningham-South, 20. Alex Dombrandt, 21. Danny Care, 22. Marcus Smith, 23. Elliot Daly
Ireland team to face England:
Ireland XV: 15. Hugo Keenan, 14. Calvin Nash, 13. Robbie Henshaw, 12. Bundee Aki, 11. James Lowe, 10. Jack Crowley, 9. Jamison Gibson-Park, 1. Andrew Porter, 2. Dan Sheehan, 3. Tadhg Furlong, 4. Joe McCarthy, 5. Tadhg Beirne, 6. Peter O'Mahony, 7. Josh van der Flier, 8. Caelan Doris
Replacements: 16. Ronan Kelleher, 17. Cian Healy, 18. Finlay Bealham,19. Iain Henderson, 20. Ryan Baird, 21. Jack Conan, 22. Conor Murray, 23. Ciaran Frawley
Farrell preparing for 'one hell of a battle'
Ireland boss Andy Farrell insists under-fire England remain capable of representing one of the ultimate tests in world rugby ahead of a tantalising Twickenham showdown.
Amid ongoing criticism of their performances, Borthwick's hosts are battling to stay in title contention after suffering a 30-21 Calcutta Cup defeat to Scotland last time out.
Englishman Farrell has little interest in the negativity surrounding his native country and is preparing for "one hell of a battle" on Saturday.
"I've no doubt that England would have loved to have put the best performance out against Scotland and come away with the victory there," he said.
"But I've no doubt now that over the last two weeks that concentrates their mind to have another chance to have a crack at us.
"You expect them to be at their best and if they're at their best you expect them to be as hard as anyone in world rugby to beat."
England were two minutes away from reaching the World Cup final in October but have struggled to fully convince since Borthwick succeeded Eddie Jones in December 2022.
"I don't get involved with the criticism at all," continued Farrell. "I don't look at it.
"I look at the individuals the way that they're playing, the coaching staff that they got, the plan that they've got, a fantastic side that is going to be preparing to give it everything they've got at the weekend, so that makes them unbelievably dangerous.
"We just prepare for them to be at their best and if that's the case it's going to be one hell of a battle."
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