On 8 August 2017, Van Niekerk successfully defended his 400 metres world title at the 2017 World Championships in Athletics in London with a time of 43.98 seconds. Two days later he finished second in the 200m in a time of 20.11 seconds at the World Championships. He became the first South African athlete to land two individual sprint medals at a single meet.
On 31 October 2017, Van Niekerk participated in a celebrity funded rugby match that was sponsored by FC soccer. During this match, he unfortunately made an inverted cut and tore his anterior cruciate ligament (ACL). He began treatment immediately after surgery and due to this injury, he was unable to attend any meets during the year of 2018. Wayde van Niekerk has been in intense rehabilitation throughout 2018, to prepare himself for the beginning of the 2019 season and 2020 Tokyo Olympics. On 31 May 2019, it was announced that he would run at the IAAF Diamond League event in London in July, his first major race since his comeback from injury.
Van Niekerk married Chesney Campbell on 29 October 2017. He is the cousin of South African World Cup-winning rugby union and rugby sevens player Cheslin Kolbe. He first started using his speed while playing rugby in junior school in Cape Town. He and his cousin, Kolbe, were on the same team. More than 12 years later they were both in the South African Olympic Team in Rio, with Kolbe playing in the Sevens.