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The La Yarada aquifer is the primary water resource for municipal, irrigation, and industrial uses in the semi-arid Tacna, Peru. Presently, over-pumping has caused severe groundwater management problems, including the abandonment of saline water wells. This study presents multivariate analysis and chemical–isotopic trends in water to investigate seawater intrusion and hydrogeological processes affecting water quality. The chemical and isotopic analysis of water samples, collected in two campaigns in the dry (August 2020) and wet (November 2020) seasons, together with the 1988 data, were evaluated with a mixing model, cluster, and factor analysis. The hydrochemical and isotopic mixing model suggested the formation of a wedge with 20% seawater intrusion. The heterogeneity of piezometric map isolines corroborates the wedge formation associated with the groundwater movement. The spatial distributions of factors, FA1 and FA2, suggest two processes of seawater front movement: dispersion (diffusion) of chemical elements and different types of water mixing, respectively. At the edge of the La Yarada aquifer, the water head was relatively low, permitting seawater and freshwater mixing. On the other hand, along the sea-land boundary, the water head of the La Yarada aquifer was relatively high, avoiding seawater and freshwater mixing; however, the chemical species were migrating from the seawater to the groundwater due to the diffusion processes. The cluster 4 samples are in the region corresponding to the isotopic mixing process represented by the FA2, while cluster 4 describes the chemical diffusion process represented by the FA2. Thus, the integrated approach is helpful to assess the seawater intrusion mechanisms in coastal aquifers in a semi-arid region.