An understanding of pollutant processes in rivers under different hydrological conditions is essential to assess its long-term evolution. This is especially relevant in Mediterranean rivers during rain events, when most of the water, suspended particulate matter (SPM), and pollutants are delivered. This study investigates the hydrochemical changes and pollutant fluxes in the Odiel River (SW Spain) during rainy conditions. For this purpose, high-resolution sampling (6 h) was performed to monitor dissolved and total concentrations of pollutants. During the rises in discharge, most dissolved elements had decreased concentrations due to the dilution effect of runoff waters and Fe precipitation processes. However, the particulate concentrations of some elements (As, Fe, Pb, Cr, Ti, V, and Ba) increased due to Fe-rich sediment remobilization, and to a lesser extent, direct precipitation. A two end-member mixing model applied to the collected data showed that the contribution of nonaffected waters was ∼85%–98% of the total discharge, highlighting the importance of mining lixiviates in the deterioration of Odiel water quality. An innovative methodology was applied to estimate dissolved and total pollutant loads, based on the relationships between dissolved concentrations and electrical conductivity (EC), and total concentrations and river flow. The importance of particulate metal transport during rain events in the Odiel River was significant. The total transport of Fe was 37 times higher than dissolved Fe, was almost 7 times higher for Pb, and 5 times higher for Cr, while As (1.1 t) was totally transported by particulate matter.