This event is stacked with talent, however, and 21-year-old 6ft 5in Bahamian Steven Gardiner looked equally impressive as he slowed to the line before winning his heat in 44.75.
Makwala’s 20-year-old teammate Baboloki Thebe won his heat in 44.82, and Jamaica’s Nathon Allen was another winner in 44.91.
Van Niekerk, who set a world record of 43.03 in winning his Olympic gold from lane eight in Rio, has a best of 43.62 this season, but he was clearly intent on starting conservatively given the range of his ambitions here.
A little burst of speed down the final straight put him ahead in the second heat, and the after-burners were off again immediately as he wound down to the line, looking around him as he did so. The 25-year-old walked away with an expression of satisfaction. London is going to be a marathon, not a sprint, for this sprinter.
Makwala was followed home in his heat by two-time world champion LaShawn Merritt, who clocked 45.00 from the unfamiliar position of lane nine. One lane inside him, Britain’s double European champion Martyn Rooney could only manage sixth place in 45.75, and failed to move through – although fellow Briton Matthew Hudson-Smith was a non-automatic qualifier after clocking 45.31.
Gardiner’s heat also saw qualification for the aptly named Wilbert London III of the United States, in 45.10, with Ireland’s Brian Gregan taking the third automatic place in the semi-finals in 45.37.
There was big noise in the third of the men’s 400m heats as Dwain Cowan, son of local coach Lloyd Cowan, surfed home on the support to take the third automatic qualifying place in 45.39 in a race won by 20-year-old medal contender Baboloki Thebe of Botswana in 44.82.
Also in the mix – 18-year-old Jamal Walton of the Cayman Islands, twice Pan American U20 champion, who moved through with a time of 45.05 that was just 0.06 off his personal best.
Mike Rowbottom for the IAAF