"Obviously a great day for the team," said Handscomb after his superb knock of 105.
"The bowlers have been great. I think tomorrow is about getting those first two wickets as quickly and cheaply as we can."
Pakistan wicketkeeper Sarfraz Ahmed showed defiance wanting in his team mates to be unbeaten on 31 at stumps, with tail-ender Mohammad Amir eight not out.
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Bruised after an opening day in which Australia piled on 288-3, Pakistan's seamers battled hard to drag their side into the game, but their batting team mates froze in the flood-lights of the final session.
Having moved to 43-1 after a cautious first hour, Pakistan lost five for 13 in a hurry as Mitchell Starc, Josh Hazlewood and Jackson Bird combined in a devastating pace assault.
Hazlewood and Starc had three wickets apiece, with Bird grabbing two for a miserly seven runs from his nine overs.
Starc struck first in the fifth over to remove Azhar Ali for five when the opener edged a lead-footed drive to the slips where Usman Khawaja dived forward and to his left to take a fine, low catch.
Number three batsman Babar Azam and opener Sami Aslam dug in for an hour before Hazlewood had Babar caught behind for 19.
Younus Khan was caught behind for a duck off Hazlewood and captain Misbah-ul-Haq (4) and Ashad Shafiq (2) joined him in the dressing room shortly after.
Wahab Riaz and Yasir Shah managed only one run apiece before Sarfraz and Amir showed fight in their late 30-run stand.
Although Wahab and Amir earlier finished with four wickets apiece to limit Australia to 429, it was another poor day in the field for Pakistan, with two dropped catches.
Handscomb, however, needed no reprieves in his determined 240-ball knock.
Sharing in a 172-run partnership with captain Steve Smith, the 25-year-old rookie's innings was all the more impressive as wickets tumbled around him.
He hammered leg-spinner Yasir Shah over the long-on boundary for six to move to 97, then completed his ton in style, smashing a square drive off seamer Amir for four.
He was bowled after tea by Wahab, chopping onto his stumps, but Pakistan were further frustrated by a feisty 10th wicket stand of 49 runs between Nathan Lyon (29) and Bird (19 not out).
(Reporting by Ian Ransom in Melbourne, editing by Sudipto Ganguly)
