Abstract Cadmium red is the name used for denoting a class of twentieth century artists’ pigments described by the general formula CdS 1− x Se x . For their vibrant hues and excellent covering power, a number of renowned modern and contemporary painters, including Jackson Pollock, often used cadmium reds. As direct band gap semiconductors, CdS 1− x Se x compounds undergo direct radiative recombination (with emissions from the green to orange region) and radiative deactivation from intragap trapping states due to crystal defects, which give rise to two peculiar red-NIR emissions, known as deep level emissions (DLEs). The positions of the DLEs mainly depend on the Se content of CdS 1− x Se x ; thus, photoluminescence and diffuse reflectance vis–NIR spectroscopy have been profitably used for the non-invasive identification of different cadmium red varieties in artworks over the last decade. Systematic knowledge is however currently lacking on what are the parameters related to intrinsic crystal defects of CdS 1− x Se x and environmental factors influencing the spectral properties of DLEs as well as on the overall (photo)chemical reactivity of cadmium reds in paint matrixes. Here, we present the application of a novel multi-length scale and multi-method approach to deepen insights into the photoluminescence properties and (photo)chemical reactivity of cadmium reds in oil paintings by combining both well established and new non-invasive/non-destructive analytical techniques, including macro-scale vis–NIR and vibrational spectroscopies and micro-/nano-scale advanced electron microscopy mapping and X-ray methods employing synchrotron radiation and conventional sources. Macro-scale vis–NIR spectroscopy data obtained from the in situ non-invasive analysis of nine masterpieces by Gerardo Dottori, Jackson Pollock and Nicolas de Staël allowed classifying the CdS 1− x Se x -paints in three groups, according to the relative intensity of the two DLE bands. These outcomes, combined with results from micro-/nano-scale electron microscopy mapping and X-ray analysis of a set of CdS 1− x Se x powders and artificially aged paint mock-ups, indicated that the relative intensity of DLEs is not affected by the morphology, microstructure and local atomic environment of the pigment particles but it is influenced by the presence of moisture. Furthermore, the extensive study of artificially aged oil paint mock-ups permitted us to provide first evidence of the tendency of cadmium reds toward photo-degradation and to establish that the conversion of CdS 1− x Se x to CdSO 4 and/or oxalates is triggered by the oil binding medium and moisture level and depends on the Se content. Based on these findings, we could interpret the localized presence of CdSO 4 and cadmium oxalate as alteration products of the original cadmium red paints in two paintings by Pollock. Graphical abstract