The giant lock sustained an ankle injury on club duty in France over the weekend ruling out the 2.03m tall, 135kg heavyweight.
The Wallabies have lost both of their matches so far — against England and Italy on Saturday — and are likely to need to pull off an improbable pair of victories against Ireland on Saturday and France on November 22 to snag a top-seed spot for the home-hosted global tournament.
However, Skelton was hurt playing for La Rochelle against Toulon in the Top 14 and Australia have said in an injury update he would be "unavailable for the team's final two tests of 2025."
Veteran James O'Connor has joined the squad in Dublin as flyhalf cover.
"James would probably add a bit of freshness," head coach Schmidt said at the weekend
Ireland will be without Jamie Osborne after he sustained a shoulder injury in the weekend win against Japan.
Osborne, who started at full-back on Saturday and in the previous week's defeat to the All Blacks in Chicago, was forced off in the second half of the 41-10 win over Japan.
The 23-year-old, who had covered for first-choice full-back Hugo Keenan, will also miss the November 22 clash with world champions South Africa in Dublin.
Canberra-born former Brumbies wing Mack Hansen (foot) and centre Stuart McCloskey (adductor) have both linked back up with the Irish squad.
Head coach Andy Farrell will announce his match-day party on Thursday. Centre Garry Ringrose and Leinster team-mate Josh van der Flier are both hoping to prove their fitness after respective hamstring strains kept them out against Japan.
with AP
