It will be the first time O'Gara has led the national side, pipping provincial colleague and captain Paul O'Connell to the job.
O'Connell has filled the role in O'Driscoll's absence in the past but the Lions lock has been overlooked as Ireland seek a third successive victory at Twickenham.
Geordan Murphy has been pencilled in at full-back after nearing rehabilitation from his Achilles problem.
Murphy missed out against Wales with the injury he sustained on club duty for Leicester and faces a fitness test later in the week to confirm his selection.
His return forces Rob Kearney, who deputised at Croke Park on Saturday, back onto the left wing, with Tommy Bowe switching over to his preferred position on the right.
As expected, Shane Horgan of Leinster has been shifted to inside centre in response to O'Driscoll's torn hamstring.
Ulster's Andrew Trimble moves a place down the line to outside centre to accommodate Horgan, with the duo forcing Ireland's third new-look midfield of this year's Six Nations.
Twickenham may have been a happy hunting ground for Ireland in recent times but defeat on Saturday would represent their worst performance in the championship since 1999.
O'Sullivan revealed O'Connell was not disgruntled at the decision to hand O'Gara the captaincy.
He said: "The call was made on the basis Paul has been out for a while and has only one game of Six Nations rugby under his belt this season.
"I want him to focus on leading the pack and his own display. Paul was happy with the rationale behind the call.
"Ronan has captained Munster this year and I see it as spreading of the load.
"He's an experienced player who is well capable of organising the team. He's a senior guy."
Murphy's fitness will be monitored throughout the week and O'Sullivan admitted a doubt still hangs over the Leicester full-back.
He said: "Geordan trained this morning and there was no reaction but the nature of the problem means that it could flare up."