The Japanese teenager, who grew up in Long Island, was never in danger against former world number one Kerber, winning a one-sided contest 6-3 6-1 despite some late nerves.
"When we were little, we would come to the U.S. Open every year. And even to practise, sometimes I would play here," the 19-year-old Osaka, who has dual nationality, told a news conference.
"So the site feels really familiar to me... It's nostalgic every time I come here, so I'm always really happy to play here."
Yet, Osaka felt nervous against Kerber in the 23,771-seat Arthur Ashe Stadium, having lost to American Madison Keys in the third round of the U.S. Open last year after leading 5-1 in the third set.
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"I was so nervous on the last point. I just barely returned the serve," said Osaka, whose father is Haitian and mother is Japanese.
"I just really didn't want to play a long point on the last one, so I was really glad when she made an error.
"When I stepped on the court and I heard all the people and I saw how big the stadium was, I got a little bit freaked out, but I tried to hold it in."
It was, however, Osaka's aggressive style, more than Kerber's mistakes, that won her the match and the youngster, who could play French Open champion Jelena Ostapenko if she reaches the fourth round, can look ahead with confidence.
"Moving forward, I feel like I know that I can play with the top players now, so I don't have to be as nervous as I was today," she said in a warning to her next opponent, Swedish qualifier Rebecca Peterson or Czech Denisa Allertova.
(Reporting by Julien Pretot; Editing by Christian Radnedge)
