The Wa'ergang section in South China has been proposed as a potential Global Stratotype Section and Point (GSSP) for the base of Stage 10, the uppermost stage of the Cambrian System. In this study, high-resolution C-isotopic compositions are reported and we identified three large negative δ13C excursions, namely N1, N2 and N3, at Wa'ergang. The N1 is located just above the First Appearance Datum (FAD) of Lotagnostus americanus, corresponding to the possible base of the Proconodontus posterocostatus conodont Zone. The N2 was identified within the Micragnostus chuishuensis trilobite Zone and the Proconodontus muelleri conodont Zone. The N3 is located in the lowermost part of the Leiagnostus cf. bexelli – Archaeuloma taoyuanense trilobite Zone or Eoconodontus conodont Zone. The N1 and N2 can be correlated with the negative δ13C excursions preceding the Top of Cambrian Carbon Isotope Excursion (TOCE) observed globally. The N3 can be correlated with the TOCE or the HEllnmaria–Red Tops Boundary (HERB) Event. The inter-basinal correlation of N1 and L. americanus strongly supports that the base of Stage 10 may be best defined by the FAD of L. americanus. We also used a box model to quantitatively explore the genesis of the negative δ13C excursions from South China. Our numerical simulations suggest that weathering of the organic-rich sediments on the platform, probably driven by intermittent sea level fall and/or the oxygenation of the Dissolved Organic Carbon (DOC) reservoir in seawater, may have contributed to the generation of the negative δ13C excursions observed in the Stage 10 at Wa'ergang in South China.