<p>Lead (Pb) contamination in mining tailings from Zaruma, Ecuador, represents an environmental concern due to its toxicity, persistence, and potential mobility under changing physicochemical conditions. This study evaluated Pb mobilization from mining tailings mediated by a <i>Bacillus safensis</i> group strain under controlled laboratory conditions. A central composite design (CCD) was applied to assess the influence of initial pH, temperature, incubation time, and solids concentration, while kinetic modeling, pH evolution analysis, apparent Gibbs-energy-based assessment, and generalized additive modeling (GAM) were used to interpret the process. Maximum Pb mobilization reached 1278.76 mg kg⁻¹, equivalent to 96.51% release, at pH 5.75, 31 °C, 14.5 days, and 0.015% solids. Pb release kinetics were best described by the shrinking core model (<i>R</i>² = 0.99), suggesting diffusion through an apparent product layer as the main rate-limiting step during later stages. pH evolution followed an exponential decay model with plateau (<i>R</i>² = 0.99), indicating progressive microbial acidification and subsequent stabilization. AICc-based GAM comparison selected the two-predictor pH–temperature interaction model as the final parsimonious structure, with 62% explained deviance and reduced overfitting risk under the limited sample size. The apparent Gibbs-energy-based assessment indicated that Pb mobilization was governed by microbial activity, pH evolution, and mass-transfer conditions rather than by global reaction spontaneity alone. These results suggest that the <i>Bacillus safensis</i> group strain can substantially influence Pb mobility in Zaruma tailings under favorable low-solid laboratory conditions, although validation at higher solids loadings and Pb recovery from the liquid phase are required for practical application.</p>