The critical environmental situation in the region of southwestern Siberia (Komsomolsk settlement, Kemerovo region) is the result of the intentional displacement of mine tailings with high sulfide concentrations. During storage, ponds of acidic water with incredibly high arsenic (up to 4 g/L) and metals formed on the tailings. The application of chemical methods to treat these extremely toxic waters is implemented: milk of lime Ca(OH)2, sodium sulfide Na2S, and sodium hydroxide NaOH. Field experiments were carried out by sequential adding pre-weighed reagents to the solutions with control of the physicochemical parameters and element concentrations for each solution/reagent ratio. In the experiment with Ca(OH)2, the pH increased to neutral values most slowly, which is contrary to the results from the experiment with NaOH. When neutralizing solutions with NaOH, arsenic-containing phases are formed most actively, arsenate chalcophyllite Cu18Al2(AsO4)4(SO4)3(OH)24·36H2O, a hydrated iron arsenate scorodite, kaatialaite FeAs3O9·8H2O and Mg(H2AsO4)2. A common specificity of the neutralization processes is the rapid precipitation of Fe hydroxides and gypsum, then the reverse release of pollutants under alkaline conditions. The chemistry of the processes is described using thermodynamic modeling. The main species of arsenic in the solutions are iron-arsenate complexes; at the end of the experiments with Ca(OH)2, Na2S, and NaOH, the main species of arsenic is CaAsO4−, the most toxic acid H3AsO3 and AsO43−, respectively. It is recommended that full-scale experiments should use NaOH in the first stages and then Ca(OH)2 for the subsequent neutralization.