Opening batsman David Warner continued his hot run of form when he made 130 to lead Australia to 353/6. It was Warner's sixth century in his last 11 innings in Sydney, including his hundred before lunch in the third Test against Pakistan in January.
It was also his fifth century in 13 ODIs innings this season, matching Matthew Hayden's Australian record.
After combining in a 92-run opening partnership with Usman Khawaja (30), Warner added 120 with captain Steve Smith (49) for Australia's second wicket to set the tone of the innings.
Warner and Smith were out within two balls of each other in the same over bowled by Hasan Ali as Australia's innings briefly faltered and it slipped from 212/1 to 213/3.
But Travis Head (51) and Glenn Maxwell (78) then added a century partnership from 63 balls to restore Australia's momentum.
Maxwell was out to the last ball of the innings after reaching his half century from 34 balls and taking his 78 runs from only 44 deliveries with 10 fours and a six.
Pakistan, on the other hand, could not achieve the target despite a tough fight.
Facing a daunting run chase against an Australian attack refreshed by the return of paceman Mitchell Starc and leg-spinner Adam Zampa, Pakistan lost all the wickets at 267.
Pakistan will play the final match against Australia at Adelaide on Thursday.
Australia XI: Warner, Khawaja, Smith (c), Head, Handscomb, Maxwell, Wade (wk), Starc, Cummins, Zampa, Hazlewood.
Pakistan XI: Azhar (c), Sharjeel, Babar, Hafeez, Malik, Akmal, Rizwan (wk), Imad, Amir, Hasan, Junaid
Umpires: Chris Gaffaney (NZL) and Mick Martell (AUS)
Third umpire: Chettithody Shamshuddin (IND)
Match referee: Jeff Crowe (NZL)