Pressure is sure to mount on Nigeria coach Stephen Keshi as they followed a shock 3-2 home loss to Congo on Saturday with another uninspiring performance.
The defending African champions have now won just one of their last 11 matches and were particularly disappointing in a World Cup campaign that led the Nigerian government launching an investigation into the country's football federation.
Ighodaro Osaguona went closest for Nigeria but his header was nodded off the line by Eric Mathoho 10 minutes from time.
The best chance of the match fell to South Africa substitute Tokelo Rantie in the 84th minute but Nigeria goalkeeper Austin Ejide kept him out with a smart save.
South Africa headed into the match in good spirits after coach Shakes Mashaba's new-look side comfortably beat Sudan 3-0 on Friday.
A big crowd was in attendance in Cape Town but they were left disappointed by what was a poor game in which both sides struggled in the final third.
In a first half bereft of chances, Oupa Manyisa went closest when his shot was blocked after Mandla Masango stormed down the right.
Half-time substitute Rantie made an impact for the hosts and after Andile Jali set him free, the forward fired into the side netting on the hour-mark.
Ogenyi Onazi then curled just wide for Nigeria, who were denied from taking the lead by Mathoho's headed clearance after Musa's cross was met by Osaguona.
Nigeria could have been made to pay with six minutes left as Sibusiso Vilakazi played in Rantie.
But the forward, who was one-on-one with Ejide, could not beat the goalkeeper as both sides were forced to share the spoils.
South Africa have not beaten Nigeria since February 2004.
Congo now top Group A in AFCON qualifying after a 2-0 win over Sudan, also on Wednesday.
South Africa sit second with four points from two matches, with Nigeria three points off the pace in third.
