The Capetonian, who last raced competitively in September at the Gala dei Castelli in Switzerland, won the race at the Athletics Central North Western Open Track & Field Meeting in a time of 45.92 seconds despite slipping out of the blocks.
The meet was the first national meet organised on South African soil since the country's government relaxed restrictions on training and competitions in the country two days ago.
In February, before global health restrictions were tightened against coronavirus, van Niekerk won a university-level 100m on a grass track in Bloemfontein – that was his last race on South African soil. A planned international comeback in August in Italy was disrupted when he tested positive for the coronavirus.
"Not fully satisfied"
Van Niekerk explained on social media that his lack of racing meant he had been unable to judge where he was physically.
"With me not being fully satisfied with my comeback this year due to being diagnosed with Covid-19 and not being able to compete, I’m grateful to Athletics Northwest for hosting an event for athletes to compete competitively again," he wrote.
The event, he said, would "give me a great indication to see where I am at in my training and what needs to be done to get into a positive momentum physically and mentally towards 2021."
Despite the postponement of Tokyo 2020 to 2021, the 28-year-old said there were positives for him as he sought to reach his peak once more, as he was before he suffered a freak knee injury playing a charity rugby game in 2017.
In April, he exclusively told the Olympic Channel that not only did he have a return to top form in mind, but he intends to lower his world record under 43 seconds.
"I am hungrier than before," he said.
"I still believe I can go sub-43. I can go way better than what I have in 100m and 200m, that’s where my mind was before the injury and that’s where my mind is at for the future."