Global metabolic and transcriptional reprogramming is a common event in plant abiotic stress responses, however, the relevant molecular mechanisms remain largely unknown. Here, we characterized the physiological function and molecular mechanism for the rice UGT706F1. We found that UGT706F1 can be potently induced by high temperature. Its overexpression can markedly enhance the heat tolerance of rice through improving the capacity of scavenging reactive oxygen species, whereas its functional deletion results in heat sensitivity in rice. To investigate the regulatory mechanism of UGT706F1 in response to high temperature, we carried out extensive screening of the in vitro enzymatic activity of UGT706F1 and discovered that UGT706F1 exhibits broad-spectrum activity toward flavonoid compounds. Through targeted flavonoid metabolomics analysis, we further revealed that the overexpression of UGT706F1 elevated the content of diverse flavonoids and flavonoid glycosides in rice. Subsequently, via transcriptome analysis, we found that following heat treatment, the overexpression of UGT706F1 was capable of enhancing the transcriptional activity of those genes including the flavonoid synthases, heat shock factors, heat shock proteins, glutathione S-transferase, and various antioxidant enzymes. Furthermore, we identified an R2R3 MYB-type transcription factor MYB61 and demonstrated that MYB61 could directly bind the promoter of UGT706F1 and activate the transcription of UGT706F1. The overexpression of MYB61 also enhanced the heat tolerance and increased flavonoid glycosides. Overall, this study unveiled a novel pathway of the plant heat tolerance response mediated by MYB61-UGT706F1 module and identified a new UGT player for the metabolic and transcriptional regulation under high-temperature circumstance.