Relebohile Mofokeng and Jayden Adams both scored their first international goals as South Africa were made to toil for a 2-0 home win over neighbours Lesotho as they went top of Group C.
South Africa travel to neutral Abidjan to play second-placed Benin on Tuesday where coach Hugo Broos’ side could potentially open up a sizeable lead in the pool.
Nigeria claimed a first win of the qualification campaign at the fifth attempt with a 2-0 success over Rwanda in Kigali.
Victor Osimhen scored a brace to take Nigeria to six points, four behind South Africa.
Ghana, who failed to qualify for the Africa Cup of Nations in Morocco later this year, moved top of their qualification pool with a 5-0 hammering of Chad in Accra.
Antoine Semenyo, Inaki Williams, Jordan Ayew, Mohammed Salisu and Ernest Nuamah all scored for the home side, who lead Madagascar in Group I by two points.
Ivory Coast took over at the top of their pool as they claimed a narrow 1-0 win over Burundi in a game played in Morocco.