South African Olympic champion had not run competitively outside his homeland since 2017 World Championships
The South African started out of the blocks slowly in Lane 4 but powered home down the finishing straight to win in 45.58 seconds.
Van Niekerk had last run a competitive meet outside his home country at the 2017 World Athletics Championships in London when he won his second 400m world title, having been blighted by a number of different injuries since then.
In February, before global health restrictions were tightened against coronavirus, van Niekerk won a university-level 100m on a grass track in Bloemfontein. However, a planned international comeback in August in Italy was disrupted when he tested positive for the coronavirus.
Fresh off the back of his third major international championship win over 400m, van Niekerk was the man to watch going into the 2018 Commonwealth Games and leading up to Tokyo 2020.
However, in October 2017, the South African suffered a rupture of the anterior cruciate ligament in his right knee while playing in a charity touch rugby match in Cape Town.
That meant surgery, and spending the entire 2018 season sidelined while rehabbing.
The following year started brightly, with hopes that he might be able to return to defend his world title in Doha. However, another setback followed that July when he suffered a bone bruise in his knee and chose to protect it instead of risk more injury.
After making his return to running in Bloemfontein in February, van Niekerk set his sights higher.
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."
After the race, van Niekerk set his sights firmly on Tokyo.
"It was a good ice breaker, considering the circumstances I’ve had to go through the last few months, not being able to be as consistent as I’d like to be," he said according to The Citizen.
"It has been a bit of a roller coaster year, but I feel comfortable and confident for the upcoming season and the Olympic Games.
"It’s time to get back to the drawing board and start sharpening up the edges."