The geochemical and mineralogical study of the Quiulacocha tailings impoundment has shown that the hydrological connection of the three studied mine-waste systems at Cerro de Pasco (Pyrite-rich waste-rock dump Excelsior, old tailings impoundment Quiulacocha, and the active tailings impoundment Ocroyoc) is a critical concern for effective acid mine drainage (AMD) control and mine-waste management. The Quiulacocha tailings covered 114 ha, comprising 79 Mt of tailings, which contained ∼ 50 wt.% pyrite, and are located at 4340 m altitude in a tropical puna climate with about 1025 mm/a rainfall and 988 mm/a of evaporation. The tailings were partially overlain by the Excelsior waste-rock dump, which contains about 26,400,000 m3 of waste rocks that cover 94 ha and contained ∼ 60 wt.% of pyrite, which origin from a massive pyrite-quartz replacement body. Therefore, these two mine-waste deposits had a direct hydrological connection, resulting in the export of AMD produced at Excelsior towards Quiulacocha. In the Quiulacocha impoundment there are two different types of tailings recognized, that interact with the AMD from Excelsior: 1) Zn–Pb-rich tailings and 2) Cu–As-rich tailings. During the sampling, the Zn–Pb-rich part of Quiulacocha was not producing important excesses of AMD from the oxidation zone, since the pH increased to near neutral values at 1 m depth. The underlying tailings were still able to neutralize the acidity produced in the oxidation zone through sulfide oxidation by the carbonates (mainly dolomite and siderite) contained in the Zn–Pb mineral assemblage. The main source of AMD in this mine-waste system is the Excelsior waste-rock dump. Its acid seepage infiltrates into Quiulacocha forming a Fe–Zn–Pb plume with a pH 5.5–6.1 and containing up to 7440 mg/L Fe, 627 mg/L Zn, and 1.22 mg/L Pb. The plume was detected at 10–13 m depth in the stratigraphy of Quiulacocha tailings. Additionally, the AMD seepage outcropping at the base of the Excelsior waste-rock dump was channeled on the tailings surface into the Quiulacocha pond (pH 2.3), which covered the Cu–As-rich tailings. Infiltration of this Fe(III)-rich AMD increased tailings oxidation in the southwestern part of the impoundment, and subsequently liberated arsenic by enargite oxidation. Additionally, the AMD collected in the Quiulacocha pond was pumped into the active Ocroyoc tailings impoundment, where sulfide oxidation was strongly enhanced by the input of dissolved Fe(III). Therefore, the AMD management and a hydrological separation of the different mine-waste systems could be a first step to prevent further extension of the AMD problem in order to prevent increased sulfide oxidation by Fe(III)-rich solutions.