The 18-hole course on the border of the Kruger National Park has wild animals roaming its fringes and crocodiles and hippos lazing in the water features.
It has long been among Schwartzel's favourites and the former U.S. Masters champion dominated on Friday as he completed his first round with a 66 and then shot 67 in the second for an 11-under-par total at the halfway mark.
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It put him well clear of the chasing pack in the first event of the 2016 European Tour.
The 31-year-old South African, who has won three times at Leopard Creek, was out at 6.30am local time (0430GMT) to complete his first round with a birdie on the 18th after a thunderstorm suspended play late on Thursday.
Then, after a swift turnaround, he birdied six holes for a second round 67.
"I kept giving myself chances all day. I had good control of the irons and if I can fire up the putter, I can shoot even lower," Schwartzel said.
The conditions on Friday were windy and in contrast to the sweltering heat of the previous day when the golfers had to contend with temperatures close to 40 degrees Celsius.
Spain's Pablo Martin, who has won twice at Leopard Creek, is joint second on six-under with Frenchman Benjamin Hebert, Dutchman Joost Luiten and South Africa's Richard Sterne.
Englishman Eddie Pepperell shot the best round of the day with his 65 taking him to five-under.
Overnight leader Christiaan Basson, who hit an opening round 64, slumped to a 76 on the second day and is now four under-par.
Louis Oosthuizen, the highest-ranked player in the field at 15, missed the cut after shooting 76 in the second round.
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