Melatonin improves plant resistance to multiple stresses by participating biosynthesis of plant metabolites. Flavonoids, as an important family of plant secondary metabolites, are widely recognized to be involved in resistance. However, the crosstalk between melatonin and flavonoid is largely unknown. With melatonin pretreatment, we discovered the resistance of pigeon pea was significantly enhanced against salt, drought, and heat stresses. Combined transcriptome and LC-ESI-MS/MS metabolomics showed that melatonin significantly induced the enrichment of flavonoids and mediated the reprogramming of biosynthetic pathway genes. The CcF3'H family encodes an enzyme that catalyzes the biosynthesis of luteolin, with the highest upregulated expression fold in response to melatonin treatment. The transcription factor CcPCL1 directly bonded to the CcF3'H-5 promoter to enhance the transcription of CcF3'H-5. In addition, salt stress also induced the expression of CcPCL1 and CcF3'H-5. Further, through the overexpression of CcPCL1 and CcF3'H-5, salt tolerance was greatly enhanced by promoting the biosynthesis of luteolin. Overall, our results indicated that melatonin pretreatment promoted luteolin biosynthesis through the CcPCL1 and CcF3'H-5 pathways, resulting in salt tolerance in pigeon pea. Our study showed that melatonin enhanced plant tolerance to multiple stresses by mediating flavonoid biosynthesis, providing new ideas for studying the crosstalk between melatonin and flavonoids.