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.
Muguruza seemed to have the match under control after battling back from 2-4 down to win the first set, with her opponent only winning 29 per cent of her second-serve points in dropping the opener.
But the Spaniard, who was shaky on serve throughout the one-hour, 52-minute match, crumbled over the last two sets to make an abrupt exit from tennis's grass-court Grand Slam.
The 47th-ranked Van Uytvanck struck 29 winners for the match, compared to just 18 for Muguruza, and broke her opponent's serve on seven occasions.
"She played big, took a lot of risk and it worked for her. I also think that my level was not where I wanted it to be. That's also why she could develop that kind of level," Muguruza was quoted as saying by the BBC.
"It's a bit sad because I wanted to really go out there. But I think she played great and she has a very good game for this surface."
The Spaniard has been maddeningly inconsistent at Wimbledon, winning the tournament last year and reaching the 2015 final but failing to reach the third round in her other four main-draw appearances dating back to 2013.
This year's early loss was surprising because the Spaniard seemed to be poised for a deep run after a strong French Open, where she trounced Maria Sharapova in the quarter-finals before losing to eventual champion Simona Halep in the semi-finals.
Prior to Muguruza's defeat, second-seeded Caroline Wozniacki and seeds four through six -- Sloane Stephens, Elina Svitolina and Caroline Garcia -- had already been eliminated from the tournament.
Also surprising were the early exits of eighth-seeded Czech Petra Kvitova, the 2011 and 2014 champion; and the 24th-seeded Sharapova, the 2004 winner and 2011 runner-up.
Halep, the top seed, avoided the upset bug on Thursday, defeating China's Zheng Saisai 7-5, 6-0 to advance to the third round.
She and American seven-time champion Serena Williams are among a handful of favourites for the title.
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