Lesia Tsurenko 6-1 6-1 and the pair became the first Japanese man and woman to reach the semi-finals of the same grand slam.
To get to Saturday's championship match, the 20th seed will have to get past either USA 14th seed Madison Keys or Spain's Carla Suarez Navarro.
So far, with two of the three matches on hard court, Keys has won six of their seven competed sets - all within the last two years - and the main issues have come on return in these historical match-ups, with Keys holding 83.3% of service games against Osaka previously.
Keys was the runner-up to Sloane Stephens at the U.S. Open in 2017, then lost to Stephens in the French Open semifinals this year.
For Osaka, her victory is the latest milestone in a watershed year for the 20-year-old who won her first WTA Tour title in Indian Wells, Calif., in March.
Prior to this meeting, though, it is the first semi-final, between Serena Williams and Anastasia Sevastova, starting at midnight.
'I just was like "I've got to play a little better", the crowd helped me out after the first two games, ' she said of her start.
For Williams, it was more of what we've seen all Open. She recovered to win in three sets, with her opponent accusing her after the match of acting. And, when Sevastova dropped her serve at the start of the second set, she knew she was looking across the net at the best player in the world, whom the tournament recognised with a No17 seeding for the fortnight.
He played back-to-back four-setters against Karen Khachanov and Nikoloz Basilashvili before recovering from breaks down in the third and fourth sets against Thiem.
It was another hot afternoon Wednesday, with temperatures in the 30s C, but feeling much hotter due to the humidity. Nishikori, 8 years older, was like a "really big kid" who liked to play video games and have fun like her.
On Wednesday, Osaka only needed 12 winners because a whopping 31 of her other points came via unforced errors by Tsurenko.
Djokovic moved a step closer to a third championship at Flushing Meadows and 14th Grand Slam title overall by eliminating Millman 6-3, 6-4, 6-4 in the quarterfinals.
"I was, alongside many other people, anticipating the match against Federer", Djokovic said.
She said: "It means a lot".
The Japanese stars both advanced to the semi-finals at Flushing Meadows on Thursday (AEST).
Though he clawed his way back into the set, it was the 21st seed who got over the line as Cilic again imploded in a breaker.