Van der Burgh finished first in the men's 100m breaststroke final on Sunday night, securing the South Africa's first medal at the London Olympic Games.
He finished in a time of 58.46 – 0.12 seconds faster than the previous record held by Australian Brenton Rickard.
Another Australian, Christian Sprenger (58.93), finished second, and Brendan Hansen of the United States (59.49) clinched the bronze medal.
Van der Burgh had qualified for the final in emphatic style on Saturday when he won his semifinal by breaking the previous South African, African and Olympic records with a time of 58.95.
Van der Burgh's medal is South Africa's first at the London Olympics, which have so far been dominated by China.
After securing four gold medals on the first day, Chinese athletes hit paydirt once again on Sunday with wins in shooting for Guo Wenjun before synchronised divers Wu Minxia and He Zi triumphed at the Aquatics Centre.
Guo successfully defended her 10m air pistol title with a thrilling last-shot finish at the Royal Artillery Barracks to overhaul France's Celine Goberville, who had led going into the last round.
"I just focused on doing my best on the final shot," Guo said, adding: "I think everyone is good, I just never give up."
Legendary diver Wu, meanwhile, clinched her third consecutive gold medal in the 3m springboard synchronised after wins in 2004 and 2008.
In the pool, American Dana Vollmer won the women's 100m butterfly gold medal, clocking a world record of 55.98sec for a crushing victory over China's Lu Ying.
Vollmer became the first woman to break through the 56-second barrier as she added Olympic gold to the world title she claimed last year.
She bettered the previous world record of 56.06sec set by Sweden's Sarah Sjostrom on July 27, 2009 at the World Championships in Rome.
"I just relied on my strengths," Vollmer said. "Just set it up well, passed a few people and charged it home."
France's Camille Muffat won the women's 400m freestyle gold with Britain's defending champion Rebecca Adlington in third.
World champion James Magnussen dived in at the last change to reel in US veteran Jason Lezak and lift Australia into Sunday night's relay final as top qualifiers.
It was Magnussen's first swim at the Games and the "Missile" delivered on his brash confidence, clocking a sizzling 47.35 seconds to surge past Lezak (48.04).
Defending Olympic champions America were second quickest ahead of Russia and France.
While China celebrated their burgeoning gold haul, hosts Great Britain were still waiting for their first win with cyclist Lizzie Armitstead having to settle for silver in a thrilling road race won in driving rain by Marianne Vos of the Netherlands.
United States shooter Kim Rhode took the gold medal in the women's skeet, her fifth consecutive visit to the podium following medals at the Atlanta, Sydney, Athens and Beijing Olympics.
Uzbek gymnast Luiza Galiulina was provisionally suspended after testing positive for the banned diuretic furosemide, the International Olympic Committee (IOC) announced.
Galiulina underwent a drugs test on July 25, three days before the start of the women's artistic gymnastics competition.
Meanwhile, St Kitts and Nevis record sprinter Tameka Williams has been sent home from the Olympics after admitting taking a banned substance, officials said.
Williams (22) the Caribbean country's 100m and 200m record-holder, did not fail a drugs test but made the revelation during discussions over vitamins and nutritional supplements, an official told AFP.
Meanwhile, the chair of the London Olympics, Sebastian Coe, insisted most venues were full of spectators as organisers launched a probe into blocks of empty seats at some events.
Coe said unoccupied seats at some venues were due to accredited officials still working out which events to attend, but he said he had visited four events on Saturday which were full to capacity.
In other action on Sunday, the United States' collection of NBA multi-millionaires, who are expected to cruise to a successful defence of the basketball title, eased past France 98-71 in their opening game.
Over at Wimbledon, Maria Sharapova, Novak Djokovic and home hope Andy Murray were all winners on a rain-hit day. – Sapa-AFP