ZnCr–CO3 layered double hydroxide (LDH) has been prepared by a two-step process combining direct coprecipitation and anionic exchange. To investigate the influence of thermal treatment on ZnCr–CO3 LDH photocatalytic activity, the thermal decomposition of the matrix was studied by in-situ thermal X-ray diffraction and thermal analysis (TGA/DTA). The structure and the textural properties of the materials obtained upon different thermal treatment have been characterized by several techniques such as X-ray diffraction, FTIR, UV–vis diffuse reflectance spectroscopy, N2 adsorption, scanning and transmission electronic microscopy. Prior to study Orange II (OII) photodegradation, adsorption behavior of uncalcined and calcined ZnCr–CO3 LDH toward OII was studied evidencing that LDH thermal decomposition leads to a net decrease of the adsorption behavior. All the samples induce the photodegradation of OII. The compounds obtained after calcination above 600 °C display the highest photocatalytic activity attributed to the formation of well crystallized ZnO and ZnCr2O4 spinel leading to complete mineralization of OII. Optimal photocatalytic conditions were defined as 0.5 g L−1 of photocatalyst and basic pH conditions. To further highlight the oxidation process, experiments with 4-chlorophenol, which is not adsorbed on LDH surface and with isopropanol and terephthalic acid, used as HOradical dot radical trap, were carried out. In terms of photodegradation mechanism, both hydroxyl radical generation in bulk and direct interaction with hole on the surface of the photocatalysts were evidenced.