The pair put on 119 off 78 balls for the unbroken fifth wicket to help their team recover from 46-4 and surpass Australia's 164-7 with five balls to spare in a group F match of the Super Eights at the Wanderers.
Man-of-the match Misbah smashed 66 not out off 42 balls and Malik chipped in with an unbeaten 52 as Pakistan virtually assured themselves of a place in the semi-finals.
Pakistan's second win in the group, following the 33-run win over Sri Lanka on Monday, left them needing a point against Bangladesh in Cape Town on Thursday to move into the last four.
Australia, who must beat Sri Lanka on Thursday to stay in contention for the semi-finals, were left to ponder the jinx that the Wanderers ground holds for them.
It was Australia's first appearance at the historic venue since South Africa successfully chased their formidable 434 with one ball to spare in a memorable one-day international in March, 2006.
Malik and Misbah came to the crease with Pakistan tottering at 46-4