The 36-year-old shot a flawless seven-under-par 64 to move two ahead of Germany's Max Kieffer (65) who is also looking for his maiden tour title.
Austrian Bernd Wiesberger was a further shot adrift in third place after a 66. Ryder Cup pair Victor Dubuisson (69) and Martin Kaymer (69) were tied for fourth position on 207 with Britain's James Morrison (68).
"Today was really a phenomenal round," Van Zyl told reporters after finishing with a 10-under total of 203. "I felt really comfortable from tee to green and made a couple of nice putts.
"I've been in this position a couple of times and hopefully tomorrow we can pull through.
"I had surgery on both knees last year which wasn't great. You don't quite know what to expect coming out here but luckily I got off to a nice start at the beginning of the year and got the confidence building a little bit," said Van Zyl.
(Writing by Tony Jimenez, editing by Mark Meadows)
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