Opener Saim Ayub smashed 56 off 37 balls while Babar Azam chipped in with an unbeaten 50 to power Pakistan to a strong 207-6 at the Gaddafi Stadium.
Shadab Khan, who hit five sixes, provided the late flourish with 46 off 19 balls.
Australia, who rested several members of their World Cup squad from the tour, folded for 96 in 16.5 overs to succumb to their biggest defeat in T20 Internationals.
Australia spinner Adam Zampa, who sustained a groin injury, did not bat.
Faced with a steep chase, Australia wobbled early in their pursuit.
Pakistan speedster Shaheen Afridi bowled rival captain Mitchell Marsh in the first over and dismissed Matt Renshaw in the third to leave Australia reeling at 16-3 inside three overs.
Marcus Stoinis (23) and Cameron Green (22) tried to put Australia's chase back on track before left-arm spinner Mohammad Nawaz (5-18) intervened.
Nawaz removed both the set batters and ran through Australia's middle and lower order to set up Pakistan's massive victory.