A semi-finalist last year, Tiafoe charged to within one victory of another last-four showing in New York with an impressive 6-4 6-1 6-4 win over the inspired wildcard.
Hijikata's service speed was noticeably down from his previous three rounds, with Tiafoe having little trouble picking it off and breaking the 22-year-old six times in the two-hour encounter.
Utterly dominant, the American conceded just 13 points on his own serve in setting up a quarter-final with unseeded countryman Ben Shelton, who beat Tommy Paul in four sets.
Hijikata's first foray to the last 16 at a grand slam earned the Sydneysider $US284,000 ($A440,000) and a world rankings boost from 110 to a career-high 81.
"It just gives me a lot of belief," he said.
"It's my first time making the fourth round of a major. I feel like a lot of people go a long time in their career, their whole career, kind of not making a second week of a slam and to be able to do that, in my head it's a pretty big deal.
"That's a pretty big goal of mine and to kind of tick that off so early in my career, I'm pretty happy with that."
Hijikata is now in line for a direct entry to the Australian Open in January and gives Australia nine men in the top 100 even without the injured Nick Kyrgios.
Only powerhouses the USA (11) and France (11) have more.
Alex de Minaur, provisionally slated to rise to No.11, Max Purcell (43) and Chris O'Connell will also climb to career-best rankings after the Open, while Alexei Popyrin (45) and Aleksandar Vukic (50) both hit their highest position last month.
"It's been pretty cool to see how all the other Aussie guys and girls have been supporting me and each other," Hijikata said.
"We've got a really good group of guys at the moment. I feel like we are all pushing each other to get better."
But while chuffed about his surprise charge to the last 16, Hijikata craves more.
"I'm happy with the results I've had and take a lot of confidence away from it, but at the same time, I know I have to get a lot better," he said.
"There's a lot of things I need to improve if I want to be able to kind of match it with the top guys. That's my end goal. I'm not satisfied being where I am at the moment."
Hijikata's exit leaves de Minaur as Australia's last remaining singles hope at Flushing Meadows.
The 24-year-old plays third-seeded 2021 US Open champion Daniil Medvedev on Tuesday (AEST) for a place in the quarter-finals.
