Sio, hailed as the saviour of the Australian scrum after his performances at last year's World Cup, was comprehensively overpowered by England's Dan Cole and ended up in the sin-bin in last weekend's 39-28 first test defeat.
James Slipper is promoted off the bench to replace Sio, while Sekope Kepu also steps up from the replacements to start instead of Greg Holmes at tighthead.
Otherwise, Cheika has kept faith with the tactics if not the personnel of the team that started in Brisbane.
Sean McMahon will start at number eight in place of David Pocock, who fractured an eye socket in the opening match and was ruled out for the series.
The dynamic McMahon, like Pocock, is a specialist openside flanker and will operate alongside number seven Michael Hooper in the back row.
"Based on last weekend’s performance, we decided that we wanted some new combinations for Saturday’s game," Cheika said in a news release.
"Sean never takes a backwards step while James and Sekope add plenty of test match experience."
Sam Carter comes into the second row for lineout caller Rob Simmons, who suffered a back injury in the opening test, and will lock with ACT Brumbies team mate Rory Arnold.
With a third ACT Brumbie in skipper Stephen Moore throwing in, Cheika is clearly hoping club familiarity will add some solidity to the Australia lineout.
There are no changes to the backline with winger Rob Horne having recovered from a knock to the head and Cheika sticking with his inexperienced, 200-kg plus centre partnership of Tevita Kuridrani and Samu Kerevi.
On the bench, where Cheika named 11 players with three to be omitted, a third openside flanker in Liam Gill earned a recall, while Wycliff Palu and Ben McCalman offer their coach the choice of two more traditional number eights.
Australia must win in Melbourne to stay alive in the series. The final test takes place at the Sydney Football Stadium on June 25.
Team: 15-Israel Folau, 14-Dane Haylett-Petty, 13-Tevita Kuridrani, 12-Samu Kerevi, 11-Rob Horne, 10-Bernard Foley, 9-Nick Phipps, 8-Sean McMahon, 7-Michael Hooper, 6-Scott Fardy, 5-Sam Carter, 4-Rory Arnold, 3-Sekope Kepu, 2-Stephen Moore (captain), 1-James Slipper
Replacements (Three to be omitted): Tatafu Polota-Nau, Toby Smith, Greg Holmes, James Horwill, Dean Mumm, Wycliff Palu, Ben McCalman, Liam Gill, Nick Frisby, Christian Lealiifano, Luke Morahan
(Reporting by Nick Mulvenney in Sydney; Editing by John O'Brien)
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