The 33-year-old Western Force half-back is one of four changes to the starting side that defeated England 20-14 at Twickenham last Sunday, with Drew Mitchell and Stephen Moore promoted from the bench, while blindside flanker Scott Higginbotham returns from a two-game suspension.
Sheehan will earn his seventh cap in Florence with coach Robbie Deans moving Nick Phipps to the bench as he looks to freshen up his playing group for the team's penultimate match of a gruelling 2012.
Mitchell swaps roles with Digby Ioane, with the latter reverting to the bench after he returned from injury in a starting position at Twickenham.
Moore earns his first start since the second Bledisloe Cup match in August, taking over from Tatafu Polota-Nau who has been demoted to the bench.
Deans said the changes are designed to bring energy to the playing group as the Spring Tour moves into its third Test, and reiterated it was not a case of sending a weakened team to play a weaker opponent.
"If you look at the men who are coming in, they are all seasoned Test players," Deans said.
"Drew (Mitchell) is one of the most experienced Test wingers in Australian history; Stephen Moore is our most capped hooker, while Scott (Higginbotham) was the Test incumbent in his position until the suspension.
"No-one should doubt the impact that Brett Sheehan has made since he has joined the squad either.
"Nick (Phipps) did well last weekend against England and he is still in a position to contribute this weekend but Brett has worked hard and has earned this opportunity."
New Zealand crushed Italy 42-10 in Rome last weekend but Deans said the last-quarter blowout belied a much closer contest.
"They (Italy) are not the first side to have suffered in that manner against the All Blacks," he said.
"If you look at the game in its entirety as I'm sure (Italy coach) Jacques (Brunel) will have done, there was a lot of good in it for them.
"I've no doubt they will be looking forward to another opportunity this weekend.
"It has been a notable feature of recent performances that the Italians are looking to play with a bit more width and use the ball more, expanding on their usual strength in the physical exchanges."
Australia: Berrick Barnes; Nick Cummins, Adam Ashley-Cooper, Ben Tapuai, Drew Mitchell; Kurtley Beale, Brett Sheehan; Benn Robinson, Stephen Moore, Ben Alexander, Sitaleki Timani, Nathan Sharpe, Scott Higginbotham, Michael Hooper, Wycliff Palu.
Replacements: Tatafu Polota Nau, James Slipper, Sekope Kepu, Dave Dennis, Liam Gill, Nick Phipps, Mike Harris, Digby Ioane.