The 47th-ranked Van Uytvanck, who captured a title earlier this year in Budapest, recorded her first career Top 10 win and advances to a third-round matchup with 28th seed Anett Kontaveit. Six of the women's top 10 seeds are already gone.
The American fought back from a set and two breaks down only to falter near the end as she lost to Russian qualifier Evgeniya Rodina 7-5, 5-7, 6-4 in the third round.
Elsewhere, Rafael Nadal overcame two time warnings and Novak Djokovic shrugged off a knee problem to battle into the third round.
Muguruza edged the first set after trailing by a break, but Van Uytvanck produced some fine strokes to even the match and then completely took over in the third with a double break before completing the match with a triumphant serve.
"I may have looked calm but inside I was dying".
"She played big, took a lot of risk and it worked for her". The 24-year-old, who is also campaigning against bullying, said coming out as gay hadn't lifted a weight off her shoulders, or helped her compete better, neither was she looking to be a role model.
He faces Alex de Minaur next.
Also through is last year's surprise victor at Roland Garros - 12th seed Jelena Ostapenko, defeating Belgian Kirsten Flipkins, 6-1, 6-3.
Cilic blew a two-set lead in his 3-6, 1-6, 6-4, 7-6 (7/3), 7-5 loss to Argentina's Guido Pella, ranked at 82.More news: Oil prices climb on tightening U.S. market
In the opening set, Liu broke the powerful lefty three times and won four games in a row to take the set, but Kerber rallied to win the second.
Cilic, the 2014 US Open champion, had been expected to mount a strong challenge for the Wimbledon title after winning the grass-court warm-up at Queen's Club two weeks ago. "If schedule is out they can not change it but anyway I would like to talk to them about why they did it because I think now we are not in rush, but I will try to do my best to be ready and show my best", said the 22-year-old Siniakova.
Isner hit 64 aces and saved two match points in his victory. I was just missing some balls, some easy balls, giving him a chance to come back. "It's more hard for me to understand what's going on", said 11-time French Open champion Nadal, who is chasing an 18th major.
Van Uytvanck duly served out the encounter easily, despite saying she was "dying" inside.
Swiss Stan Wawrinka suffered a shock 7-6 (7) 6-3 7-6 (6) defeat by world number 133 Thomas Fabbiano in a match that resumed on Thursday after rain halted play on Wednesday.
"I had (the) pressure (a) little bit of (possibly) losing that (first) set but I didn't panic. I mean, that's what they decided", Muguruza said.
The British No 1 reached the semi-finals at the All England Club previous year, but hard-hitting Slovakian Cibulkova produced a ruthless display to end Konta's hopes 6-3 6-4 on Thursday.
Del Potro's 6-4, 6-1, 6-2 win set-up a 3rd round clash with France's Benoit Paire.