Pakistan were all out for 148 in reply to Australia's first innings total of 556-9 declared on day three of the second Test at the National Stadium in Karachi on Monday.
Skipper Babar Azam's 36 was the highest score for the hosts.
Meanwhile, Mitchell Starc was the pick of the Australia bowlers, claiming 3-29.
Australia, after declaring their first innings, reduced Pakistan to 100 for seven at tea to seize control of the second Test. Australian skipper Pat Cummins smashed three sixes in his unbeaten 34 off 36 balls against a jaded Pakistan attack on a slow track.
Pakistan had reasons to feel let down by their in-form openers who showed poor judgment to depart either side of the lunch break.
Abdullah Shafique made 13 before chasing a non-existent single only to be run out.
Imam, who smashed twin hundreds in the drawn series opener in Rawalpindi, paid the price for his needless aggression in the first over after the lunch break.
The bespectacled left-hander stepped out against Nathan Lyon only to chip a head-high catch to Cummins at mid-on to depart for 20.
Starc then claimed two in two to rock Pakistan.
The left-arm quick lured Azhar Ali (14) into driving a full and wide delivery and Cameron Green grabbed the edge at second slip.
Starc followed it with a searing yorker to trap Fawad Alam lbw for a duck.
Mohammad Rizwan somehow denied Starc a hat-trick but looked pretty much a sitting duck during his 13-ball stay.
Dropped in the slip by Steve Smith off Cummins, Rizwan got another life in the very next ball when an lbw decision against him was overturned.
It did not really matter though as Cummins returned to dismiss Rizwan caught behind in his next over.
Starc owed his third wicket to Alex Carey who was convinced he had taken a catch from Sajid Khan even though the bowler himself was not sure and the umpire did not think so either.
Carey convinced Cummins to review the original not-out decision and Sajid had to go after replays confirmed an edge.
Australia are on their first tour of Pakistan since 1998, having previously refused to tour on security reasons.