The news follows on from Amakhosi's Nedbank Cup semi-final exit at the hands of Free State Stars on Saturday evening.
Komphela was appointed head coach before the start of the 2015/16 campaign as a replacement for current Bafana Bafana coach Stuart Baxter, who won two Absa Premiership titles, the MTN8 and Nedbank Cup.
Amakhosi supporters were expecting Komphela to continue where Baxter left off, but the former Ea Lla Koto coach lost two knockout competitions finals in the first few months in the job. It went from bad to worse for Komphela, who was never accepted by Amakhosi supporters. The Nedbank Cup exit means Komphela and Amakhosi will finish a third straight season with no silverware in the cabinet.
According to manager Bobby Motaung, the decision for Komphela to make an exit was made before the game against Stars.
Amakhosi confirmed the coach's decision shortly after the game, posting on their official Twitter account:
Breaking News: Steve Komphela has resigned with immediate effect as head coach of Kaizer Chiefs! More news to follow #KCOneTeam
— Kaizer Chiefs (@KaizerChiefs) April 21, 2018