Marler and Itoje replace Mako Vunipola (Saracens), who moves to the bench, and Joe Launchbury (Wasps), who was deemed unfit to play on Wednesday, in two changes to the 15 that started in the 9-40 victory over Italy in Rome.
Elsewhere Wasps centre Elliot Daly is included as a replacement for the first time. Courtney Lawes (Northampton Saints) also makes the bench having been recalled to the squad.
England head coach Eddie Jones said:
“I have been pleased with the attitude the squad have shown during a comprehensive two weeks of training. Everyone is pushing hard to be in contention so there were some tight calls on selection.
“Joe Marler made a big impact off the bench in Rome and will start at loose-head with Mako Vunipola finishing the game. Joe Launchbury is unlucky to miss out through injury; Maro Itoje is selected as a result and we’re pleased for him.
“Elliot Daly has worked hard this week and is now ready for a place in the 23. He can provide cover in several positions in the back line.
“Playing our first game at Twickenham after two away fixtures will be huge for us. We’re determined to put in a strong performance against a clever Irish side who are the benchmark of European rugby.”
England match-day 23 to face Ireland
15. Mike Brown (vice captain, Harlequins, 45 caps)
14. Anthony Watson (Bath Rugby, 17 caps)
13. Jonathan Joseph (Bath Rugby, 18 caps)
12. Owen Farrell (vice captain, Saracens, 37 caps)
11. Jack Nowell (Exeter Chiefs, 12 caps)
10. George Ford (Bath Rugby, 19 caps)
9. Ben Youngs (Leicester Tigers, 54 caps)
1. Joe Marler (Harlequins, 39 caps)
2. Dylan Hartley (captain, Northampton Saints, 68 caps)
3. Dan Cole (Leicester Tigers, 58 caps)
4. Maro Itoje (Saracens, 1 cap)
5. George Kruis (Saracens, 12 caps)
6. Chris Robshaw (Harlequins, 45 caps)
7. James Haskell (Wasps, 64 caps)
8. Billy Vunipola (vice captain, Saracens, 23 caps)
16. Jamie George (Saracens, 5 caps)
17. Mako Vunipola (Saracens, 29 caps)
18. Paul Hill (Northampton Saints, 1 cap)
19. Courtney Lawes (Northampton Saints, 44 caps)
20. Jack Clifford (Harlequins, 2 caps)
21. Danny Care (Harlequins, 55 caps)
22. Elliot Daly (Wasps, uncapped)
23. Alex Goode (Saracens, 20 caps)