Van Niekerk, the World 400m Champion, shattered his 100m Personal Best by 0.50 to win the Free State title in Bloemfontein in 9.98 seconds.
In the process, the 23-year-old athlete became the first man in the world to run under 10 seconds in the 100m event, 20 seconds in the 200m (19.94) and 44 seconds in the 400m (43.48).
Elsewhere at the weekend, long jumper Luvo Manyonga was in superb form in Pretoria, winning the Gauteng North title in his specialist event with a best effort of 8.30m.
Continuing his comeback from a lengthy layoff, after being suspended from the sport for recreational drug use, Manyonga confirmed he was on the rise again by setting a new Personal Best.
In Potchefstroom, two-lap specialist Caster Semenya also stuck up her hand at the North West Championships.
Chopping another chunk off her 400m Personal Best after setting a career record of 52.21 a week earlier, she charged around the track in 51.47 seconds to qualify for the one-lap event at the 2016 Rio Olympics.
With the Provincial Championships completed, athletes will now focus on the three remaining legs in the ASA Night Series, as well as the National Championships in their various age groups, as the domestic season reaches full swing.
"These performances, among others, indicate that a great year lies ahead for the sport in SA," said Aleck Skhosana, the President of Athletics South Africa.
"Credit is due to the Athletes and Coaches, as well as their ASA Provinces for focussing on the core business in which they specialise. Wayde is a special athlete and we wish him an injury free season leading to the Rio Olympics. We hope to see our sprinters one day soon smashing the 9:90 seconds barrier."