Japan's Osaka came into the second-round match against fourth-seeded Ukrainian Svitolina on an eight-match winning streak that included her dream run to the Indian Wells title and a first-round triumph here over 23-time Grand Slam champion Serena Williams.
But it was Svitolina who emerged with a 6-4, 6-2 victory thanks to a solid service performance that saw her win nearly 80 percent of points on her first serve.
Svitolina saved five of six break points she faced and broke Osaka four times en route to the victory in an hour and 23 minutes.
After staving off Osaka in a close first set, Svitolina raced to a 4-0 lead in the second.
A reeling Osaka finally held serve with an ace for 4-1, but Svitolina produced an ace of her own to win the next game.
Osaka saved two match points before holding for 5-2, but she was unable to convert three break points in the next game as Svitolina sealed the win.
"Just Indian Wells, she was pretty confident," Svitolina said, adding that Osaka's win over Williams only bolstered that assurance. "It was challenging. I'm very happy the way I handled this match today and the way I was playing."
Osaka said she didn't feel any mental let-down, but she was battling physical illness that had her throwing up before the match. She never considered withdrawing, however.
"I don't think it would be right to just not play, especially after I play someone like Serena, then if you just don't play the next match -- I think that's wrong."
Svitolina next faces Australian Daria Gavrilova, a 7-6 (7/3), 6-4 winner over Germany's Andrea Petkovic.
Osaka, meanwhile, will have time to regroup after a whirlwind fortnight. The 20-year-old leaped 22 places in the rankings to number 22 in the world on the strength of her surprise Indian Wells win.
- Kvitova advances -
She conquered her nerves to beat Williams on Wednesday, another setback to the US great's return from a 13-month absence to have her first baby -- daughter Alexis Olympia.
"I think I've played more matches than I ever have back-to-back," Osaka said of the positives she has taken from her recent run of success. "I didn't really feel that tired, so that's a good thing.
"And I've played so many good players, and I've experienced a lot of new things, so I'm really happy about that."
Osaka said that "definitely playing Serena" was the highlight of the last two weeks.
"But also just the matches leading up to the (Indian Wells) final, and the final itself. Of course winning the final was really cool, (but) I've always dreamed of playing Serena so I think that's my number one."
In other second-round action on Friday, ninth-seeded Czech Petra Kvitova defeated 19-year-old Aryna Sabalenka of Belarus 7-5, 3-6, 6-3.
Kvitova, a two-time Wimbledon champion and former world number two, needed just over two hours to triumph in a match of heavy-hitters.
She set up a third-round match against American qualifier Sofia Kenin, a 3-6, 6-2 6-2 upset winner over 19th seeded Daria Kasatkina of Russia, who was runner-up to Osaka at Indian Wells last week.