Acid mine drainage (AMD), formed by the instability of sulfides, typically generates acidity and releases potentially toxic elements and sulfate to the environment, among other pollutants. An example is the group of rare earth elements (REE) that may have high toxic behavior. This toxicity leads to degradation of soils, water reservoirs and rivers, promoting serious risks for the ecosystems. So, the main goal of the present work is to study the hydrochemical properties of a system with mine-influenced waters during the rainy season, focusing on the origin, evolution/behavior, and concentration of REE. The study area is the São Domingos mining complex, located in one of the largest metallogenetic provinces in the world (Iberian Pyrite Belt), known by the evidences of AMD contamination. The obtained results reveal extraordinarily low pH (0.4), high electrical conductivity, reaching 26,200 μS/cm, and high values of sulfate and acidity. Regarding the REE, the determined concentration exceeded that observed in normal pH of neutral freshwaters by 2–3 times the order of magnitude. The results revealed that Y and Ce are distinguished in practically all sampled sites, due to its higher concentrations, with maximum values of 221.8 and 166.9 μg/L. In general, the concentrations increase as the water pH decreases. The statistical analysis indicates that REE elements may have a common origin, mutual dependence, and similar behavior during transport with typical AMD elements and composition of host rocks. Most samples show enrichment in middle REE (MREE) (Gdn/Lun), like the classic signature of AMD. In turn, colloids and AMD-precipitates may be participating in the incorporation of these elements. Therefore, due to potential risk of impacts on ecosystems, REE are a topic of relevant interest for future studies in order to assist monitoring processes and help government decisions related to water quality management.