Lead (Pb) is a toxic heavy metal posing potential harm to the environment and human health. In this study, Pb(II) adsorption performance of co-pyrolysis biochar derived from sewage sludge and gypsum (CaSO4) was first investigated. The anti-interference to environmental factors was investigated, with the underlying mechanisms being explored quantitatively. The maximum Pb(II) adsorption capacity of co-pyrolysis biochar (SSCB, 152.66 mg/g) was largely improved compared to single sewage sludge biochar (SSB, 29.95 mg/g) at a dosage of 1 g/L and initial pH of 6.0. Model analysis results indicated that monolayer sorption, chemisorption, intraparticle diffusion and endothermic processes were involved in the adsorption process. Among the tested co-existing ions, Fe2+ and NH4+ mostly disrupted the Pb(II) removal. Mineral precipitation (37.55%) and ion exchange (28.05%) were calculated as the major adsorption mechanisms (65.60%) for Pb(II) removal using co-pyrolysis biochar. SSCB showed better reusability for Pb(II) removal in 5 regeneration cycles. This work provides fundamental references for the utilization of solid wastes via co-pyrolysis to biochar for heavy metals removal towards sustainable development.