The photo-oxidation mechanism of thin-film blends based on poly(3-hexylthiophene):phenyl-C61-butyric acid methyl ester (P3HT:PCBM) upon irradiation with ultraviolet-visible light (UV-Vis) was studied. The use of deuterated P3HT, i.e., poly(3-hexyl-d13-thiophene) (P3HdT), permitted discrimination of carbon originating from the hexyl-d13 chain and carbon originating from PCBM and the nondeuterated thiophene unit. The photo-oxidation of both components of the blend was monitored using the combination of various analytical techniques to probe the bulk and the surface of the deposits. The results show that the stabilization of P3HT by PCBM is due to a morphological reorganization between P3HT and PCBM. This change occurs at a low temperature (ca. 42 °C) and increases the lifetime of the primary property, i.e., the ability of the active layer to absorb light. However, this is counterbalanced by the enhanced formation of oxidized PCBM molecules, which may act as electrons traps. It is shown that UV light is harmful for P3HT, PCBM, and P3HT:PCBM blend stabilities, even if PCBM provides a filter effect that is strongest at short wavelengths. It is proposed that the photochemical behavior of the chromophoric species involved in the chain radical oxidation of P3HT is a key characteristic in the underlying mechanism. The results obtained in this work advance the understanding of active layer stability and will help improve the design of long lifetime organic solar cells thanks to the use of cutoff filter in the substrate or encapsulation of the devices.