Acid drainage is an important water quality issue in Andean watersheds, affecting the sustainability of urban, agricultural, and industrial activities. Mixing zones receiving acid drainage are critical sites where changes in pH and chemical environment promote the formation and dissolution of iron and aluminum oxy/hydroxides. These particles can significantly change the speciation of toxic metals and metalloids throughout drainage networks via sorption, desorption, and settling processes. However, little is known about the behavior of particle size distributions (PSDs) in streams affected by acid drainage and their relationship to metal speciation. This work studied: (a) the PSDs for a wide range of mixing ratios found at a fluvial confluence affected by acid drainage, and (b) the response of PSDs and arsenic speciation to environmental changes found when the particles approach complete mixing conditions. The confluence between the Azufre River (pH ~ 2, high concentration of dissolved metals) and Caracarani River (pH = 8.6, low concentration of dissolved metals) was used as a representative model for study. Field measurements show a bimodal PSD with modal diameters of ~50 and 300 μm. At shorter distances from the junction, the smaller modes with smaller particle volumes were dominant across the stream cross‐sections. A systematic shift towards larger particle sizes and larger particle volumes occurred downstream. The analysis of laboratory PSDs for Azufre/Caracarani mixing ratios between 0.01 and 0.5 (pH from 6.2 to 2.3) showed a bimodal trend with ~15 and 50 μm characteristic diameters; larger particles formed at pH>4. When particle suspensions were transferred in laboratory experiments from very low pH to full mixing conditions (pH ~ 2.8 and mixing ratio ~ 0.25) particle sizes varied, and the dissolved arsenic concentration decreased. The observed reaction kinetics were slow compared to the time scale of advective transport, creating opportunities for engineered controls for arsenic. This work contributes to a better understanding of the chemical‐hydrodynamic interactions in watersheds affected by mining, and identifying opportunities to improve water quality at points of use.