BackgroundWatermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] is an economically important crop with an attractive ripe fruit that has colorful flesh. Fruit ripening is a complex, genetically programmed process.ResultsIn this study, a comparative transcriptome analysis was performed to identify the regulators and pathways that are involved in the fruit ripening of pale-yellow-flesh cultivated watermelon (COS) and red-flesh cultivated watermelon (LSW177). We first identified 797 novel genes to extend the available reference gene set. Second, 3958 genes in COS and 3503 genes in LSW177 showed at least two-fold variation in expression, and a large number of these differentially expressed genes (DEGs) during fruit ripening were related to carotenoid biosynthesis, plant hormone pathways, and sugar and cell wall metabolism. Third, we noted a correlation between ripening-associated transcripts and metabolites and the key function of these metabolic pathways during fruit ripening.ConclusionThe results revealed several ripening-associated actions and provide novel insights into the molecular mechanisms underlying the regulation of watermelon fruit ripening.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3442-3) contains supplementary material, which is available to authorized users.