The Leinster centre, who has had only 66 minutes of action to date in the championship with replacement appearances against France and Italy, is one of four changes made by Irish coach Declan Kidney for the trip to Edinburgh.
As the unbeaten Irish chase their first Grand Slam since 1948, Kidney has turned to some old heads to help his team see off the Scots. As well as recalling D'Arcy to the starting line-up for his 40th cap, Munster scrum half Peter Stringer returns for his 88th.
Other changes from the win over Italy see Ulster skipper Rory Best take over from Jerry Flannery at hooker and Munster's Denis Leamy replace Jamie Heaslip at No 8. Flannery and Heaslip join Paddy Wallace and Tomas O'Leary in dropping down to the replacement bench.
D'Arcy has fought back well from the broken arm that kept him sidelined for much of the early part of the season and will join his Leinster team mate Brian O'Driscoll in the Irish midfield.
They both toured with the 2005 Lions in New Zealand and now the pair will get the chance to show their collective credentials once again.
"The four guys who have come in have been doing very well in training and have a done a good job whenever they've come on," said Kidney.
"The lads who are out have done nothing wrong. The new guys will bring their own chemistry to the team and have a wealth of experience, which we'll need against Scotland."
Munster tight head prop John Hayes will become Ireland's most capped player at Murrayfield, winning his 93rd cap and eclipsing the mark set by fellow squad member Malcolm O'Kelly.
Ireland: Rob Kearney (Leinster); Tommy Bowe (Ospreys), Brian O'Driscoll (Leinster, captain), Gordon D'Arcy (Leinster), Luke Fitzgerald (Leinster); Ronan O'Gara (Munster), Peter Stringer (Munster); Marcus Horan (Munster), Rory Best (Ulster), John Hayes (Munster), Donncha O'Callaghan (Munster), Paul O'Connell (Munster), Stephen Ferris (Ulster), David Wallace (Munster), Denis Leamy (Munster).
Replacements: Jerry Flannery (Munster), Tom Court (Ulster), Mick O'Driscoll (Munster), Jamie Heaslip (Leinster), Tomas O'Leary (Munster), Paddy Wallace (Ulster), Geordan Murphy (Leicester)