<p>The middle–late Cambrian witnessed recurrent biotic crises in the aftermath of the Cambrian explosion, exemplified by the late Cambrian end-Marjuman Biomere Extinction linked to major environmental perturbations across the Guzhangian–Paibian boundary. However, the precise mechanisms underlying this biodiversity collapse remain unclear. Mercury isotopes from two slope sections in South China reveal enhanced upwelling during the late Guzhangian, followed by photic zone euxinia in the early–middle Paibian, corresponding to the two extinction phases. This mercury record suggests that initial upwelling, followed by hydrogen sulfide toxicity in shallow oceans, drove the two-stage collapse of shallow marine shelf faunas in South China. Furthermore, this study strengthens the case that the coupled positive Δ¹⁹⁹Hg (mass-independent isotope fractionation) and negative δ²⁰²Hg (mass-dependent isotope fractionation) shifts can serve as a tracer for upwelling in Precambrian–Cambrian oceans. Collectively, our mercury isotopes offer new insights into the dynamic interactions between ocean chemistry and early animal evolution in the middle–late Cambrian.</p>