Osaka set a personal milestone by securing her first grand slam semifinal, and brought some pride to her home nation by becoming the first Japanese woman to advance to the final four of a slam tournament in two decades.
In the end she made it easy, swatting aside unseeded Ukrainian Lesia Tsurenko in under an hour, 6-1 6-1.
Her compatriot Nishikori had rather a more difficult time of it in his matchup against Maric Cilic, taking five sets to oust the Croat, 2-6 6-4 7-6 4-6 6-4.
"It's always a battle with Marin," he said after securing his third US Open semifinal. "It was great tennis today."
The match was a retread of their 2014 US Open final, but with happier results for the Japanese, who has endured an injury-enforced absence for the last four months of 2017 after suffering a wrist injury in the run-up to the 2017 US Open.
'Freaking out inside'
Osaka quelled nerves in her quarterfinal appearance to put in an assured performance, only dropping a handful of points on her serve. In the end her dominance was reflected in the one-sided score.
"It means a lot," she said. "I was freaking out inside. My entire body was shaking, but I was really glad I was able to play well today."
She will meet Madison Keys on Thursday, after the American dumped out Spaniard Carla Suarez Navarro in the day's other women's quarterfinal, also in straight sets 6-4 6-3.
The Californian has dropped just a single set so far at the 2018 edition of the US slam, to Aleksandra Krunic in the third round, and has a 2-0 edge against her upcoming Japanese opponent.
"To break in both sets, having solid games there, was really important tonight," Keys said in her on-court post-match interview.
Keys' compatriot Serena Williams will match up against Anastajia Sevastova in Thursday's other semi, with the six-time champion looking to match Margaret Court's all-time record of 24 major wins -- just a year after giving birth to her first child.