Head coach Eddie Jones moves Elliot Daly from out wide to full-back, where he replaces the injured George Furbank, while scrum half Ben Youngs is recalled at the expense of Willi Heinz for what will be his 100th Test appearance, including two caps for the British and Irish Lions.
Lewis Ludlam drops out as Courtney Lawes returns in the back row, and with Mako Vunipola absent for family reasons, Joe Marler comes in at prop as Ellis Genge has to settle for a place on the bench once again.
Tuilagi's return after missing the victory over Scotland with a groin injury beefs up England's midfield, but the selection of Joseph on the wing catches the eye, given he is a centre by trade and Jones had more orthodox options.
Joseph will win a 50th England cap, while centre Henry Slade is on the bench, having not yet played this year because of an ankle problem.
England began its campaign with a defeat to France in Paris before getting the better of Scotland at Murrayfield.
They play a first home match of the tournament against an Ireland side which has beaten Scotland and Wales already, and will be seeking to stay in contention for the Grand Slam.
Jones said: "Ireland are a very good team, extremely well coached. They are a team we respect a lot. They will bring their usual physicality and under Andy Farrell they've opened up their game a little bit.
"They are a tactically smart team. [Conor] Murray and [Johnny] Sexton, who have played 170 Tests between them, at nine and 10 will manage the game well. We've got to make sure we match their physicality and their emotion on the weekend."
England: Elliot Daly; Jonny May, Manu Tuilagi, Owen Farrell (captain), Jonathan Joseph; George Ford, Ben Youngs; Joe Marler, Jamie George, Kyle Sinckler, Maro Itoje, George Kruis, Courtney Lawes, Sam Underhill, Tom Curry.
Replacements: Luke Cowan-Dickie, Ellis Genge, Will Stuart, Joe Launchbury, Charlie Ewels, Ben Earl, Willi Heinz, Henry Slade.