After Murguruza's exit the women's draw has been left wide open.
The No. 3-seeded Muguruza joined No. 2 Caroline Wozniacki, No. 4 Sloane Stephens, No. 5 Elina Svitolina, No. 6 Caroline Garcia and No. 8 Petra Kvitova on the way out so far, along with five-time major champion Maria Sharapova.
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 think she played big today", Muguruza told reporters. That's also why she could develop that kind of level.
"It was not easy", she admitted."I had pressure little bit of losing that set".
"Of course I wanted to play on the bigger court, it's always my preference but to say something now makes no sense".
"Just didn't feel so good".
Although Cilic saved two match points at 4-5 with thunderous serves, there was no such respite at 5-6 and Pella completed the job thanks to a forehand into the net from his opponent. Uytvanck, who is openly gay and in a relationship with fellow Belgian pro 20-year-old Greet Minnen, said, "I mean, I'm not sick".
The third seed's loss on Thursday is the latest in a rash of upsets in women's singles, with six of the top eight seeds out of the tournament after just four days of play, reports Efe.
Kei Nishikori (24), Japan, def. Bernard Tomic, Australia, 2-6, 6-3, 7-6 (7), 7-5.
Men's third seed Marin Cilic was Thurday knocked out of Wimbledon following a shock five-set defeat to Argentina's Guido Pella in the second round.
Van Uytvanck, who is ranked 47th in the world, stormed to a 4-2 lead in the second set and Muguruza's frustration was in full view.
Van Uytvanck, who has only got past the second round at a grand slam once before, began to find her range midway through the second set and levelled the match with a run of four successive games.
Britain's 22nd seed Johanna Konta was ousted by Dominika Cibulkova. "It seems like it's nothing major". Muguruza, meanwhile, owns two major titles, including the 2016 French Open, and was the runner-up at the All England Club in 2015.
Nick Kyrgios, seeded 15, unleashed 42 winners to see off Robin Haase of the Netherlands 6-3, 6-4, 7-5.
The Belgian, who has been open about her relationship on social media, talked about it publicly for the first time in a segment of a television sports show back home earlier in the year, where she said the couple were going to live together soon.