Chasing 264 for victory, Australia reached 3-265 with five overs to spare, with Smith (108no off 104 balls) and Handscomb (82 off 84) combining for a match-winning 183-run partnership.
The triumph gave Australia a 2-1 lead in the five-match series ahead of Sunday’s clash at the SCG.
But Thursday’s result could have been vastly different if it wasn’t for an untimely Junaid Khan no-ball in the 11th over.
Handscomb thought he was out for a duck when he was caught at slip with Australia struggling at 2-46.
As Handscomb trudged off the field, replays showed Junaid’s delivery was a front-foot no-ball.
Handscomb was unaware of the no-ball until reserve umpire Paul Wilson charged down the tunnel to tell the batsmen to turn back.
If Handscomb had gone another 10m to walk off the field, he wouldn’t have been able to return.
Handscomb’s luck didn’t stop there.
He was given another life on 10 when he was dropped at point.
Handscomb made the most of the double reprieve to guide Australia out of their early trouble.
Smith led the way with his eighth ODI century, while Handscomb proved to be a handy ally in front of 15,383 fans.
“I think I’m going to buy a lottery ticket tonight,” Handscomb said of the no-ball incident.
“As I was walking off, I started to hear the crowd going nuts, and couldn’t quite work out what was going on.
“So I looked up on the big screen and saw the no-ball. Lucky I did, because it was about three more steps before I was off the field.
“So I managed to turn around just in time.”
Handscomb wants to prove he’s more than just a one-trick pony, but he knows he faces a stiff battle to retain his spot in Australia’s ODI side for the long term.
Handscomb has enjoyed a meteoric rise on the international scene over the past two months.
The 25-year-old made an instant impact after earning a shock Test call-up in November, compiling 399 runs at an average of 99.75 in his four matches to date in the baggy green.
Handscomb is still viewed by many as a player better suited to the long form of the game.
Prior to yesterday’s ODI debut, Handscomb’s top score in domestic limited overs cricket was just 72, with an average of 31.4.
But he is determined to improve his limited-overs cricket, and he hopes his match-turning knock for Australia is the start of something special.
Handscomb said he will learn off players like Smith, David Warner, and Glenn Maxwell in a bid to become a more explosive player in one-day cricket.
“I understand my one-day record in domestic cricket isn’t great,” Handscomb said.
“I guess I just need to be able to find a way to score off more balls.
“In the longer format, you can let a lot go and wait until the ball is in your zone to hit.
“Whereas here, you need to start fabricating a few shots and making a few things up, which I’m working on. And trying to score quicker.”
Handscomb was parachuted into the one-day squad following injuries to allrounder Mitch Marsh (shoulder) and Chris Lynn (neck).
Both players are seen as crucial to Australia’s future ODI plans, and Handscomb knows he is in danger of being squeezed out at some point.
“If they had been fit, I wouldn’t be here, and this opportunity wouldn’t have occurred,” Handscomb said.
“So in that sense, I’ve been very lucky as well.
“If I keep getting an opportunity in the middle order in the ODI team, that would be great.”
Earlier, Australian wicketkeeper Matthew Wade missed the easiest of stumpings as Pakistan posted 7-263 after losing the toss.
Babar Azam scored 84 off 100 balls to equal the record as the fastest batsman to reach 1000 ODI runs, achieving the feat in just 21 innings.
Sharjeel Khan (50 off 47), Umar Akmal (39) and Shoaib Malik (39) chipped in with handy scores to lift Pakistan to a competitive total.
Paceman Josh Hazlewood led the bowling superbly in the absence of rested star Mitchell Starc, returning 3-32 from 10 overs.
Part-time spinner Travis Head collected 2-65 in a mixed outing, while paceman Billy Stanlake (1-55 off 10 overs) overcame some early nerves to put in a solid display.
Stanlake conceded 20 runs off his second over after Sharjeel cracked him for four consecutive boundaries.
The 22-year-old speedster had figures of 0-27 by that stage.
But he conceded just 28 runs from his next eight overs, snaring the wicket of Shoaib in the process.
Wade was left red faced when he missed the chance to stump Umar on one.
Umar was caught in no-man’s land after charging several paces down the pitch and missing an attempted slog of spinner Head.
But Wade failed to glove the ball, allowing Umar to scamper back into his crease.
He added another 38 runs before falling to Hazlewood.
Wade’s superior batting has allowed him to overtake fellow wicketkeeper Peter Nevill in the Test pecking order.
But Wade’s latest mistake with the gloves could send some concerns into the Australian camp ahead of the four-Test tour of India, where the dustbowl pitches will prove to be an even bigger challenge for wicketkeeping.
Pakistan coach Mickey Arthur said the two missed chances to get Handscomb out cheaply cost his team dearly.
“Our only chance of really exerting pressure was to take early wickets, and we nearly had that right,” Arthur said.
“They would have been three down for 40-odd.
“And where we’re at as a team, we just can’t afford those little lapses, so very disappointing.”
Australia lead the series 2-1 heading into Sunday’s clash at the SCG.
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