Van Niekerk ran 100m in 9.98 seconds in Bloemfontein on Saturday to add to his 19.94 personal best over 200m and 400m world title-winning 43.48.
The 23-year-old was helped by a legal 1.5m/sec tailwind and 1,300m altitude.
"Wow! Finally reaching my dream of sub 10," Van Niekerk wrote on Instagram alongside a video of the race.
Former world and Olympic 200m and 400m champion Michael Johnson wrote on Twitter: "Sub 10, sub 20, sub 44. That's crazy. Great things could be ahead for Dwayne."
Van Niekerk will only run the 400m at the Olympics in Rio this summer.