Gillespie, a veteran of 71 Tests and 97 one-day internationals for Australia, leads a young team announced Monday, which also includes Test contenders, opening batsman Phil Jaques and fast bowler Shaun Tait.
Gillespie and vice-captain Cameron White are among five players with Australian international experience, along with Jaques (two Tests, four ODIs), Mark Cosgrove (three ODIs) and Tait (two Tests).
"To be given the opportunity to lead such a young and exciting side in what will be my first PM's XI game is a fantastic honour and one that I am really looking forward to," Gillespie said in a Cricket Australia statement Monday.
"To be the leader of the first side to take on England at the start of what is shaping as a great series is a real privilege and one that I am sure will be a fantastic moment for the team and the Australian public."
Six members of the team -- batsmen Jaques, Cosgrove, Shaun Marsh and Travis Birt and bowlers Tait and Ben Hilfenhaus -- played for Australia A during the recent series against India A, New Zealand A and Pakistan A in Darwin and Cairns.
Chairman of selectors Andrew Hilditch said the PM match was important for England and Australia's search for younger playing talent.
"It's a great honour for any Australian cricketer to be selected to play for the Prime Minister's XI," Hilditch said in the statement.
"This is an important game for England in the build-up to the Ashes series and gives a great platform to some of our younger talented players.
"Jason Gillespie has been one of Australia's greatest servants in the past decade and many of his finest moments have come against England.
"Apart from Jason we have picked a young side and we hope they display their talents against this high quality international side.
"There are some young players with international experience like Phil Jaques and Mark Cosgrove but we have some exciting young batting talent as well in Shaun Marsh, Travis Birt, Adam Voges and Tim Paine.
"Young bowlers Shaun Tait and Ben Hilfenhaus impressed during the Australia A series earlier in the year and also during their stints at the Centre of Excellence. They are both very much in our thoughts moving forward".
This will be the 10th time a Prime Minister's XI has played England, with the home team's record standing at six wins and three losses.
Prime Minister's XI - Jason Gillespie (captain), Cameron White, Travis Birt, Mark Cosgrove, Ben Hilfenhaus, Phil Jaques, Shaun Marsh, Tim Paine, Adam Ritchard, Shaun Tait, Adam Voges, Mark Divin (12th man)