D'Arcy, who celebrated his 25th birthday on Thursday, was ruled out of contention following a test on his hamstring strain in Dublin yesterday.
That means coach Eddie O'Sullivan is minus his two lynchpin midfielders for what could prove to be his fifth straight win over the Scots since taking over in 2002.
Both D'Arcy's and O'Driscoll's replacements were named yesterday - with their Leinster colleague Shane Horgan moving from the right wing to outside centre, and Ulster's Kevin Maggs coming into the match-day 22, to take the number 12 jersey.
Munster lock O'Connell - touted by many as a possible Lions skipper this summer in New Zealand - dons the armband for a second time.
The 25-year-old - who led the Irish to a 35-17 defeat to France in his first game in charge, when O'Driscoll was also out with hamstring damage - will be making his 26th Test appearance at Murrayfield.
NEC Harlequins' full-back Gavin Duffy also moves up to the replacements' bench, with Girvan Dempsey replacing his Leinster team mate Horgan out wide.
O'Sullivan said: "We gave Gordon a chance but it didn't work out.
"In terms of the risk element, it was a sensible precaution. He should be fine for the next game but we do not want to tempt fate."
He added: "We have been practising with this line-up through the week just in case."
Ireland's next opponents are England - who will come to Lansdowne Road on February 27, trying to gain retribution for last season's 19-13 loss at Twickenham - the ending of the World Champions' 22-game winning run in London.
RBS SIX NATIONS CHAMPIONSHIP: Saturday, February 12Scotland v Ireland, Murrayfield, 4.00pm
(15) Chris Paterson(14) Simon Danielli(13) Andy Craig(12) Hugo Southwell(11) Sean Lamont(10) Dan Parks(9) Chris Cusiter(1) Tom Smith(2) Gordon Bulloch (Capt)(3) Gavin Kerr(4) Stuart Grimes(5) Scott Murray(6) Jason White(7) Jon Petrie(8) Allister Hogg
(16) Robbie Russell
(15) Geordan Murphy(14) Girvan Dempsey(13) Shane Horgan(12) Kevin Maggs(11) Denis Hickie(10) Ronan O'Gara(9) Peter Stringer(1) Reggie Corrigan(2) Shane Byrne(3) John Hayes(4) Malcolm O'Kelly(5) Paul O'Connell (Capt)(6) Simon Easterby(7) Johnny O'Connor(8) Anthony Foley
(16) Frankie Sheahan(17) Marcus Horan(18) Donncha O'Callaghan(19) Eric Miller(20) Guy Easterby(21) David Humphreys(22) Gavin Duffy
Referee: Joel Jutge (France)