Six of Australia's eight tries came from front-row forwards with hooker Josh Nasser, loosehead Angus Bell and replacement rake Brandon Paenga-Amosa also crossing.
Flanker Charlie Cale and skipper Harry Wilson chipped in with late scores for the back row and scrumhalf Ryan Lonergan and replacement flyhalf Ben Donaldson combined to kick all eight conversions.
There were also fine performances from winger Max Jorgensen and flanker Carlo Tizzano, but new coach Les Kiss will have been unimpressed with some of his team's execution and defence in the first half.
"A team like Japan, if you're not up for it, they really make you pay," said Wilson.
"I was really proud of the group in that second half. We stepped it up, and we put on a great performance. I guess we went through the front door. We were physical and we had a lot more spark."
Japan scored first-half tries through Harry Hockings, Naoto Saito and Dylan Riley but were kept pointless after the break to fall to a ninth loss in nine games against Australia going back to 1975.
Coach Eddie Jones might take comfort from the amount of pressure his team were able to put on the Australians at times, as they had in the closer 35-32 loss last week.
"It was a good, tough, really hard battle," said Japan skipper Warner Dearns.
"We put a real emphasis on trying to move them around and play a bit of our fast rugby. I think we did it well in the first half, but we couldn't keep it going in the second half."
Japan reprised the expansive rugby that impressed in Osaka from the start but it was Australia who opened the scoring in the seventh minute through Nasser, who finished from close range after a flowing backline move.
Australian-born Hockings hit back for Japan five minutes later with a charge down of Ryan Lonergan's clearance kick but the Wallabies were back ahead in the 17th minute when tighthead Tupou bulldozed over the line.
Japan scrumhalf Saito cut the deficit with a try from a quickly taken penalty in front of the posts and the visitors went ahead when centre Riley stretched over the line to touch down, finishing off a slick attacking move.
Australia were playing some expansive rugby themselves and they were soon back in the Japan 22-metre line with Tupou crashing through tackles to score his second try and give the Wallabies a 21-17 halftime lead.
Bell extended Australia's advantage with another try from close range 11 minutes into the second half and a mazy break from flyhalf Carter Gordon allowed De Lutiis to mark becoming the 1,000th Wallaby in some style.
Cale went over the line on the back of a dominant scrum in the 73rd minute and number eight Wilson and Paenga-Amosa put a gloss on the scoreline after Japan had lost replacement hooker Mamoru Harada to a yellow card.