Fit-again full-back Keenan replaces Ciaran Frawley in the only change to Andy Farrell's starting XV after overcoming the knee issue that forced him to miss the 31-7 win over Wales.
Lock Ryan, who has been reduced to a peripheral role during the championship, suffered a "freak" bicep injury in training on Wednesday and will sit out the trip to Twickenham, in addition to next week's finale against Scotland.
"I think it would be a boost for any side in world rugby," head coach Farrell said of the return of Keenan. "He's a world-class full-back.
"It's testament to him and it's no shock to us that he's been able to get himself back to this position to be involved this weekend as he's been unbelievably diligent over the last few weeks to make that happen."
Ulster second row Iain Henderson has recovered from a dislocated toe to take Ryan's place on the bench.
Ryan was a strong contender to succeed Johnny Sexton as Ireland captain following the World Cup but the emergence of Leinster team-mate Joe McCarthy has limited him to just one start during this year's tournament.
Prop Finlay Bealham and the versatile Frawley join Henderson among the replacements, with Oli Jager, who has a knee problem, and centre Stuart McCloskey dropping out of the match-day 23.
Garry Ringrose is fit following a shoulder injury but must wait for his first international appearance since the World Cup due to the impressive form of midfield pair Robbie Henshaw and Bundee Aki.
Reigning champions Ireland, who are chasing successive Grand Slams on the back of bonus-point wins over France, Italy and Wales, could retain their title with a game to spare if they win in London.
Steve Borthwick's England, who reached the World Cup semi-finals last year, have faced heavy criticism for their underwhelming performances, with wins against Italy and Wales followed by a defeat by Scotland.
Englishman Farrell is braced for "one hell of a battle" against "unbelievably dangerous" opponents who are seeking to respond to their Calcutta Cup defeat to Scotland.
"I don't get involved with the criticism at all," he said of England.
"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.
"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.
"If they're at their best, you expect them to be as hard as anyone in world rugby to beat."
Ireland team:
Hugo Keenan; Calvin Nash, Robbie Henshaw, Bundee Aki, James Lowe; Jack Crowley, Jamison Gibson-Park; Caelan Doris, Josh van der Flier, Peter O'Mahony (capt); Tadhg Beirne, Joe McCarthy; Tadhg Furlong, Dan Sheehan, Andrew Porter
Replacements: Ronan Kelleher, Cian Healy, Finlay Bealham, Iain Henderson, Ryan Baird, Jack Conan, Conor Murray, Ciaran Frawley
Coach: Andy Farrell (ENG)
