Cassava is an important staple crop in tropical and sub-tropical areas. As a common farming practice, cassava is usually cultivated intercropping with other crops and subjected to various degrees of shading, which causes reduced productivity. Herein, a comparative transcriptomic analysis was performed on a series of developmental cassava leaves under both full sunlight and natural shade conditions. Gene expression profiles of these two conditions exhibited similar developmental transitions, e.g. genes related to cell wall and basic cellular metabolism were highly expressed in immature leaves, genes involved in lipid metabolism and tetrapyrrole synthesis were highly expressed during the transition stages, and genes related to photosynthesis and carbohydrates metabolism were highly expressed in mature leaves. Compared with the control, shade significantly induced the expression of genes involved in light reaction of photosynthesis, light signaling and DNA synthesis/chromatin structure; however, the genes related to anthocyanins biosynthesis, heat shock, calvin cycle, glycolysis, TCA cycle, mitochondrial electron transport, and starch and sucrose metabolisms were dramatically depressed. Moreover, the shade also influenced the expression of hormone-related genes and transcriptional factors. The findings would improve our understanding of molecular mechanisms of shade response, and shed light on pathways associated with shade-avoidance syndrome for cassava improvement.