Rob Kearney returns from knee injury to start the game at full back for the first time since November, while Fergus McFadden and Paddy Wallace form a new centre partnership with both Andrew Trimble and Luke Fitzgerald named on the wings, and Tomás O'Leary starting at scrumhalf.
The recently departed Munster player Tony Buckley will pack down with Tom Court and Sean Cronin in the front row, with his former colleague Donnacha Ryan starting alongside Cullen in the second row.
The backrow includes 50 times capped player Denis Leamy, Niall Ronan and new cap McCarthy.
Jones and Flannery join Marcus Horan, John Hayes and Mick O'Driscoll in the replacments.
Ireland take on Scotland in Murrayfield on Saturday August 8th, ko 2.15pm.
Ireland Team & Replacements:
15 - Rob Kearney (UCD/ Leinster)
14 - Andrew Trimble (Ballymena/Ulster)
13 - Fergus McFadden (Old Belvedere/ Leinster)
12 - Paddy Wallace (Ballymena/ Ulster)
11 - Luke Fitzgerald (Blackrock College/ Leinster)
10 - Jonathan Sexton (St. Mary's College/Leinster)
9 - Tomas O'Leary (Dolphin/ Munster)
1 - Tom Court (Malone/Ulster)
2 - Sean Cronin (Leinster)
3 - Tony Buckley (Sale)
4 - Donnacha Ryan (Shannon/Munster)
5 - Leo Cullen (Blackrock College/Leinster) Captain
6 - Mike McCarthy (Buccaneers/ Connacht)*
7 - Niall Ronan (Shannon/ Munster)
8 - Denis Leamy (Cork Constitution/Munster)
16 - Jerry Flannery (Shannon/ Munster)
17 - Marcus Horan (Shannon/Munster)
18 - John Hayes (Bruff/Munster)
19 - Mick O'Driscoll (Cork Constitution/ Munster)
20 - Kevin McLaughlin (St Mary's College/ Leinster)
21 - Isaac Boss (Terenure College/ Leinster)
22 - Felix Jones (Shannon/ Munster)*
N.B.*Denotes uncapped player