The previous widest winning margin by 'Bafana Bafana' (The Boys) was 5-0 at home to Guatemala in a friendly match as the republic prepared to host the 2010 World Cup.
South Africa scored three times in four minutes midway through the first half with a Nigel Hoareau own-goal followed by goals from captain Thulani Hlatshwayo and Lebo Mothiba.
A string of saves from goalkeeper Romeo Barra prevented South Africa going further ahead until Percy Tau and substitutes Dino Ndlovu and Teboho Mokoena netted in a late burst.
Mokoena scored the record-creating sixth goal two minutes into stoppage time with a close-range header off a cross at Soccer City stadium.
The one-sided affair matchday 3 affair in Group E came as no surprise as South Africa are ranked 73rd in the world -- 116 places above the Seychelles.
Only a few thousand watched the mismatch in heavy rain despite the public broadcaster not screening the qualifier because of a financial dispute with the national football body.
Matches involving 'Bafana Bafana' used to draw 80,000 crowds, but poor results in recent years has seen a dramatic fall-off in attendances.
South Africa have seven points from three matches and Libya four and Nigeria three from two in a three-team chase for two places at the 2019 Cup of Nations in Cameroon.
Nigeria, who suffered a shock matchday 1 home loss to South Africa, host Libya later Saturday in Uyo.
In Kampala, Uganda cruised to a 3-0 victory over Lesotho that moved them three points clear of Cape Verde at the top of Group L.
Emmanuel Okwi opened and closed the scoring with a goal in each half and Farouk Miya converted a penalty to give the 'Cranes' a two-goal half-time advantage.
Uganda have seven points halfway through the six-round qualifying competition, Cape Verde four and Lesotho and Tanzania two each.
Another eight qualifiers are scheduled for Saturday.