Pakistan were 382 for eight and trailing Australia by 107 runs at stumps on the fourth day of the day-night first Test at the Gabba on Sunday.
Asad Shafiq was unbeaten on 100 with Yasir Shah on four.
Earlier in the day, a rash shot from key batsman Younis Khan opened the door for Australia to push on for victory.
The 39-year-old veteran had kept the Australian bowlers at bay and loomed as his team’s last major hope after the dismissals of Azhar Ali and skipper Misbah-ul-Haq.
But the 112-Test campaigner fell to an ill-judged reverse sweep off spinner Nathan Lyon, the ball ballooning off the back of his bat for Steve Smith to take an easy catch nearing the dinner break.
At the interval, the Australians were five wickets away from victory in the series opener with the tourists at 203 for five. Asad Shafiq was on 13 with first-innings topscorer Sarfraz Ahmed not out at 17, who went on to make 24 before being bowled out by Mitchell Starc.
Australia have yet to lose at the Gabba in 27 Tests stretching back to 1988.
Pakistan’s hopes of salvaging the Test had hinged largely on the ability of their elder statesmen Younis and Misbah to occupy the crease.
But Misbah was caught behind off Jackson Bird for five to complete a low-scoring match after his four in the first innings and Younis followed just 18 minutes later.
Starc persisted with a short-pitched plan after a 90-minute storm delay at tea. It finally paid off when Azhar attempted to flick a rising ball down to fine leg only to edge to Matthew Wade.
Azhar faced 179 balls for his 71 and put on 91 runs for the third wicket with Younis. Azhar and Younis had batted through the first session to thwart the Australian bowlers.
Younis took 20 balls to get off the mark with a streaky shot through the slips cordon to the boundary.
The highest winning run chase in the fourth innings at the Gabba stands at 236 for seven by Australia against the West Indies in 1951.