British & Irish Lions half-back Murray has failed to shake off his shoulder problem and will be replaced in the number nine jersey by Kieran Marmion.
Iain Henderson comes in for Devin Toner while Jared Payne replaces Rob Kearney in the other two changes to the Irish starting line-up from the side that lost to Wales in Cardiff last time out.
Ireland head coach Joe Schmidt claims he was not willing to risk starting Murray against the English and hopes the changes to the side will see them deny Eddie Jones' side back-to-back Grand Slam titles.
He said: "We just felt if we lost him [Murray] early in the game we would be vulnerable.
"Iain Henderson came off the bench and did really well last week. Between Donnacha Ryan and Dev [Toner] we just wanted to give him a chance to start. Donnacha also did well last week, so it was just trying to get that balance.
"Rob Kearney has got a knee injury and is unavailable to be selected. It probably won't be too long but needs a bit of further investigation."