Geordan Murphy returns to the Ireland team at full-back after missing the November internationals due to a shoulder injury.
Murphy, who won his last cap against Wales last March, lined out for Leicester over the weekend and comes into the side for the injured Rob Kearney.
Leinster's Jonathan Sexton has been selected at out-half, for his first start since November's victory over South Africa.
In the forwards, long-serving prop John Hayes will win his 100th cap for Ireland as part of a front row that sees Ulster's Rory Best come into the side in place of the suspended Jerry Flannery.
Hayes, now 36, is the first Irish player to reach 100 Test caps for his country and he joins an illustrious list of players worldwide who have attained such a milestone.
The final change to the starting line-up is Donncha O'Callaghan, who has recovered from a knee injury and replaces Leo Cullen.
O'Callaghan is returning to the side for the first time since the game against South Africa in November, linking up once again with his Munster colleague Paul O'Connell in the second row.
Connacht's Sean Cronin joins the matchday 22 for the first time in an RBS 6 Nations Championship game, taking the back-up hooker role.
Meanwhile, Tony Buckley, Shane Jennings and Andrew Trimble have also been added to the replacements bench.
IRELAND Team & Replacements (v England, RBS 6 Nations Championship, Twickenham, Saturday, February 27, kick-off 4pm):
15 - Geordan Murphy (Leicester Tigers)
14 - Tommy Bowe (Ospreys)
13 - Brian O'Driscoll (UCD/Leinster) (capt)
12 - Gordon D'Arcy (Lansdowne/Leinster)
11 - Keith Earls (Young Munster/Munster)
10 - Jonathan Sexton (St. Mary's College/Leinster)
9 - Tomas O'Leary (Dolphin/Munster)
1 - Cian Healy (Clontarf/Leinster)
2 - Rory Best (Banbridge/Ulster)
3 - John Hayes (Bruff/Munster)
4 - Donncha O'Callaghan (Cork Constitution/Munster)
5 - Paul O'Connell (Young Munster/Munster)
6 - Stephen Ferris (Dungannon/Ulster)
7 - David Wallace (Garryowen/Munster)
8 - Jamie Heaslip (Naas/Leinster)
16 - Sean Cronin (Buccaneers/Connacht)
17 - Tony Buckley (Shannon/Munster)
18 - Leo Cullen (Blackrock College/Leinster)
19 - Shane Jennings (St. Mary's College/Leinster)
20 - Eoin Reddan (Lansdowne/Leinster)
21 - Ronan O'Gara (Cork Constitution/Munster)
22 - Andrew Trimble (Ballymena/Ulster)