Van Niekerk, who set a new 400m world record of 43.02sec at Rio Olympics last August, stunned his opponents by running a devastating final curve to cross the line in 43.98 seconds. Van Niekerk's lead in home straight was so big that he even eased up 20m from the line.
Bahamas Steven Gardiner took the silver in 44.41sec, while Sudan-born Qatari Abdalelah Haroun claimed bronze in 44.48.
Van Niekerk will return to track tomorrow when he competes in 200m semi finals.
Men's 400m Final Results
1 Wayde VAN NIEKERK RSA 43.98
2 Steven GARDINER BAH 44.41
3 Abdalelah HAROUN QAT 44.48 SB
4 Baboloki THEBE BOT 44.66
5 Nathon ALLEN JAM 44.88
6 Demish GAYE JAM 45.04
7 Fred KERLEY USA 45.23
Isaac MAKWALA BOT DNS