Bafana Bafana could only manage a point in their opening 2010 FIFA World Cup Brazil™ qualifier in Phokeng, prompting the South African Football Association (SAFA) to take swift action.
A SAFA statement read: "Drawing in the last 15 minutes of the game made us realise we had to act now."
Mosimane's assistant Steve Komphela will take charge of the side's next two games - against Botswana in another qualifier on Saturday and then the international friendly against Gabon later this month.
Mosimane took over from Carlos Alberto Parreira in August 2010 and leaves with a record of five wins, seven draws and three defeats from his 15 games in charge.
Moroka Swallows coach Gordon Igesund is the favourite to succeed him on a permanent basis.