Sheehan, who made his international debut six years ago, replaces Nick Phipps in the No 9 shirt, while Scott Higginbotham returns at blindside flank and Drew Mitchell replaces Digby Ioane on the wing.
Hooker Stephen Moore returns to the starting line-up in place of Tatafu Polota Nau, joining props Ben Alexander and Benn Robinson in a front row that held up well in the 20-14 win over England but is sure to be tested to the limits by Italy.
Higginbotham was left out of the original tour party after being banned for two games for headbutting Richie McCaw in last month's 18-18 draw with the All Blacks in Brisbane.
He was called over to join the squad when lock Rob Simmons was handed an eight-week suspension for a tip tackle on French flank Yannick Nyanga in Australia's 33-6 loss in Paris.
Deans said blindside flank Dave Dennis, Ioane, Polota Nau and Phipps - who all drop to the bench - had played lots of rugby this year and the side should not be viewed as weakened in any way.
"It's quite the reverse," he said in a news release. "If you look at the men who are coming in, they are all seasoned test players.
"Drew is one of the most experienced test wingers in Australian history, Stephen Moore is our most capped hooker, while Scott 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 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."
Australia have never lost to Italy and beat them comfortably at the World Cup last year on the back of a strong second-half performance.
Teams:
Italy:
TBA
Australia:
15 Berrick Barnes, 14 Nick Cummins, 13 Adam Ashley-Cooper, 12 Ben Tapuai, 11 Drew Mitchell, 10 Kurtley Beale, 9 Brett Sheehan, 8 Wycliff Palu, 7 Michael Hooper, 6 Scott Higginbotham, 5 Nathan Sharpe (captain), 4 Sitaleki Timani, 3 Ben Alexander, 2 Stephen Moore, 1 Benn Robinson
Substitutes: 16 Tatafu Polota Nau, 17 James Slipper, 18 Sekope Kepu, 19 Dave Dennis, 20 Liam Gill, 21 Nick Phipps, 22 Mike Harris, 23 Digby Ioane