Cape Verde stunned South Africa 2-1 in the 2018 Fifa World Cup Group D qualifier at the Estadio Nacional de Cabo Verde on Friday.
The defeat sees Bafana remain second on the Group D standings, while the Blue Sharks also remain fourth despite their victory.
Stuart Baxter, the Bafana head coach, made two changes from the South Africa starting line-up that faced Nigeria in the 2018 Africa Cup of Nations (Afcon) qualifier in Uyo three months ago.
Ronwen Williams replaced Itumeleng Khune in goal, while Lebogang Manyama slotted in the number 10 role just behind the main striker Tokelo Rantie, who scored as Bafana beat Nigeria 2-0.
Cape Verde head coach Lucio Antunes named a strong starting line-up which was largely made up of Portugal-based players such as Babanco, Helder Tavares and Carlos Ponck.
Bafana's Turkish-based Rantie continued his scoring form for the visitors as he broke the deadlock just 13 minutes into the encounter after the Blue Sharks defence was caught napping.
This was after the Blue Sharks had lost possession in the middle of the park and Rantie pounced onto a through ball, and he beat on rushing Cape Verde goalkeeper Vozinha to make it 1-0 to South Africa.
However, the Blue Sharks were dominating possession and they managed to level matters just after the half-hour mark following a good move by the hosts.
Tiago Almeida's good cross from the right found Nuno Rocha unmarked in the box and the latter hit the back of the net to make it 1-1 much to the delight of the home crowd.
Pressure was mounting on the Bafana defence and the home side was then awarded a penalty after Cape Verde's playmaker Ryan Mendes was fouled inside the box.
Rocha made no mistake from the spot-kick as he beat South Africa keeper Ronwen Williams to make it 2-1 to Cape Verde, who held on to their lead and they were leading at half-time.
With Bafana struggling to create chances, Baxter made a change - pulling out Lebogang Manyama, who had a quiet first half and he introduced out-and-out striker Bradley Grobler.
However, South Africa defender Erick Mathoho committed an unnecessary foul on Cape Verde defender Carlos Ponck and the towering player was sent off seven minutes after the hour-mark.
Despite their numerical disadvantage, Bafana continued to push forward in numbers, but they were left vulnerable at the back, and they nearly conceded after Tavares broke through on goal.
But Williams was alert in the goal-posts and he produced a magnificent save to deny the bulky striker, who was looking to extend the Blue Sharks' lead.
Bafana should have snatched a late equalizer in the closing stages of the encounter, but Percy Tau directed his header wide of the target from close range.
Cape Verde contained South Africa in the closing stages and they recorded a historic 2-1 win over Bafana - beating the 1996 Afcon champions for the first time.
The return leg match will be played at the Moses Mabhida Stadium in Durban next week Tuesday.