The mechanisms of red lead pigment darkening were investigated through complementary observations and analyses of naturally aged experimental wall paintings. Red lead transformation into mainly plattnerite [β-PbO2] and also anglesite [PbSO4] was established by mineralogical analyses of a micro-sample using focused X-ray diffraction and confirmed by micro-Raman spectroscopy. According to both optical and electron microscopy observations, β-PbO2 appears to have formed in the outer part of the paint surface, while PbSO4 is only located in a thin superficial layer. Structural features of plattnerite crystals were investigated using both scanning and transmission electron microscopy. Besides, red lead stability in various conditions was assessed by means of a set of physico-chemical tests applied on both raw pigment and experimental paintings. The pigment alteration is assumed to occur through the sulfation into anglesite of lead monoxide initially present in the pigment, followed by the so-called “solvolytic disproportionation” of Pb3O4. Such an alteration process is controlled by environmental parameters, namely humidity, temperature and sulfate concentration, which depend on the oxidative dissolution of atmospheric SO2 pollutant.