Owen Farrell will return to his regular flyhalf position, with George Ford dropping to the bench to allow Jonathan Joseph to start at outside centre, while Ben Te'o shifts to No 12.
Until this season, the only match England had lost since Jones took over following their first-round exit at the 2015 World Cup was when Ireland denied them a Grand Slam with a 13-9 victory in Dublin previous year.
Tensions around Saturday's London battle have been raised considerably by the emergence of a video where England boss Eddie Jones referred to the "scummy Irish".
Nathan Hughes and Courtney Lawes were already guaranteed to miss out after suffering season-ending knee injuries, but Ford, Care, Dan Cole and Joe Launchbury have all been relegated to the bench and hooker Jamie George will also be a replacement after Hartley was passed fit.
"Ben Te'o is obviously well known to us, particularly the Leinster cohort in the team, so we know what he brings and Jonathan Joseph is a freakishly talented athlete, he's going to be a handful".
Ireland, the outright tip for the Six Nations, justified faith in them by wrapping up the title with a game to spare.
But he was close to his best during Ireland's four-try 28-8 win over Scotland last time out. This suggests Stockdale is again worth backing to score this weekend.
He has reason to be confident in his team after making just one tactical change from the side that beat Scotland, rotating Iain Henderson in for Devin Toner, while Jones has hit the panic button and changed seven from his side's loss to France.
It was uploaded by Fuso to YouTube in July a year ago but has only come to light before Saturday's final round of the 2018 Six Nations when England face Ireland at Twickenham.
Ireland are by no means finished, however, as they travel to Twickenham seeking the victory that would give them a third grand slam after those of 1948 and 2009. Jones has won all 14 home matches in charge of England and he will be desperate to hold onto this record.
Should Wales lose, France will go above them and Scotland and England could too - leaving them to match last year's fifth-place finish. An opportunity to win a Grand Slam, against England, in their backyard, on Paddy's Day.