Organic micropollutants enter rivers mainly with discharges of wastewater treatment plants (WWTP) and pose a risk to aquatic ecosystems and water quality. A considerable knowledge gap exists for disentangling overlapping processes and driving conditions that control the fate of these pollutants. Thus, the aim of this study was to identify the driving parameters for attenuation of selected pharmaceuticals (carbamazepine, diclofenac, tramadol and venlafaxine) under field conditions. The presented study was performed at a small river (Ammer River, mean discharge 0.87 m3 s−1) which is hydrologically complex due to karstification, numerous artificial discharges, and engineered modifications of the channel. We applied a Lagrangian sampling scheme at two sequential river reaches. In general, for the investigated compounds and over the length of the tested reaches, the absolute net attenuation representative for 24 h was low (≤ 23% net attenuation), yet calculated half-lives were comparable to literature. Photodegradation is specifically relevant for the first river reach characterized by a higher net attenuation of the photosensitive compound diclofenac (14.5% ±11.3%) compared to the second section (9.8% ±13.7%). This is likely due to a spatial difference in canopy shading, which is supported by significant correlations (R2 ≥ 0.8) of the temporally changing ‘temperature’ and ‘solar radiation’ with time-specific degradation rate constants of photosensitive compounds for consecutive hourly water parcels. In general, the presented spatially and temporally resolved approach is a suitable tool to determine the attenuation of organic micropollutants and to narrow down the interpretation of net attenuation to a few reasonable processes.