It was the second world record at the Aquatics Centre of the day as Dana Vollmer lowered the women's 100m Butterfly mark, 24 hours after Ye Shiwen's mind-boggling effort in the 400m Individual Medley which saw the 16-year-old go faster over the final 50m than the winner of the men's equivalent, Ryan Lochte.
Van der Burgh's victory came three months after the sudden death of Dale Oen, the Norwegian world champion who died of heart failure aged just 26 at the end of April.
The 24-year-old said: 'It's a feeling I can't describe right now, it has been a lot of work in the making. Everything has paid off tonight.
'I just have to pay tribute to Alexander Dale Oen tonight, I know he has been with me this year, I think he helped me finish the race in such a strong manner.
'If there is such a thing as the perfect race, I think I swam it at the right time tonight.
'Alexander pushed me in training, it made me realise I had to go faster to win the gold medal, that is what we trained for and that is what we have achieved.'
Christian Sprenger of Australia was second (58.93) with the USA's Brendan Hansen third (59.49).
Vollmer won the 100m Butterfly in 55.98, dipping 0.08 inside Sarah Sjostrom's 2009 mark.
France shocked the USA as Yannick Agnel overhauled Lochte in the final metres to win the 4 x 100m Freestyle Relay in 3:09.93.
It was the first medal of London 2012 for Michael Phelps and his 17th overall.
He said: 'The thing about the relay is that it's the whole race (so it can't be judged on individual laps).
'At least I'm in a medal today.'
Sun Yang heads the 200m Freestyle into Day 3's finals with Matt Grevers fastest in the 100m Backstroke.
Ruta Meilutyte, just 15, is fastest through into the 100m Breaststroke with Emily Seebohm heading the 100m Backstroke.