Ajmal, who has been suspended due to an illegal bowling action, has single-handedly ruled the dry and slow tracks of Pakistan's neutral venues in the United Arab Emirates, especially at Dubai where he has 37 wickets in six Tests, three of which Pakistan won.
That includes 24 wickets in a 3-0 rout of England in 2012.
Pakistan have also lost frontline seamers Junaid Khan and Wahab Riaz -- both through knee injuries -- and have to rely on uncapped leg-spinner Yasir Shah and two-Test left-armer Zulfiqar Babar, both of whom are likely to play.
"Ajmal has left a big hole," said Misbah, who skippers a team whose last Test series win over Australia was back in 1994.
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"But we have youngsters who should grab the chance and I am confident they can."
The return of veteran batsman Younis Khan and Azhar Ali will boost Pakistan's fragile batting as they seek to remain unbeaten in a Test series in the UAE since they were forced to decamp in 2009 due to security fears in their country.
But they have dominated Pakistan, winning 13 out of the last 14 Tests against them.
Australia will hope skipper Michael Clarke, top Test run getter in 2013 with 1,093, anchors the batting after recovering from a hamstring injury sustained two months ago.