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Understanding contaminant transport through unsaturated porous media is a considerable challenge, given the complex interplay of nonlinear physical and biogeochemical processes driven by variations in water saturation. In this study, we tackled this challenge through a series of column experiments involving fine (100-300 μm) and coarse (1.0-1.4 mm) sand particles coated with birnessite (MnO₂) under variable saturation degrees. Dynamic flow experiments in sand columns revealed that desaturation altered the ability of MnO₂ in removing tetracycline (TTC), a redox-active antibiotic, yet the effect depends on the sand type and then on the saturation degree. Moderate saturation degrees in fine-grained sand columns promoted fractional and preferential water flow which favored a more acidic pH and increased dissolved oxygen levels. These conditions enhanced TTC removal, despite the reduced physical accessibility of reactive phases. In contrast, lower saturation degrees in coarse-grained sand columns induced stronger flow heterogeneity with a very small fraction of the water content participating in flow. The mobility behavior of all the columns was predicted using transport models that consider TTC adsorption and transformation, as well as dual porosity under variable water saturation degrees. This research offers valuable insights into predicting the fate and transport of redox-active contaminants in unsaturated soils and subsurface environments.