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Rice is the staple food for about half of the world population. Rice grain yield and quality are affected by climatic changes. Arguably, rice cultivars’ genetic diversity is diminished from decades of breeding using narrow germplasm, requiring introgressions from other Oryza species, weedy or wild. Weedy rice has high genetic diversity, which is an essential resource for rice crop improvement. Here, we analyzed the phenotypic, physiological, and molecular profiles of two rice cultivars (IRGA 424 and SCS119 Rubi) and five weedy rice (WR), from five different Brazilian regions, in response to heat and drought stress. Drought and heat stress affected the phenotype and photosynthetic parameters in different ways in rice and WR genotypes. A WR from Northern Brazil yielded better under heat stress than the non-stressed check. Drought stress upregulated HSF7A while heat stress upregulated HSF2a. HSP74.8, HSP80.2, and HSP24.1 were upregulated in both conditions. Based on all evaluated traits, we hypothesized that in drought conditions increasing HSFA7 expression is related to tiller number and that increase WUE (water use efficiency) and HSFA2a expression are associated with yield. In heat conditions, G_s (stomatal conductance) and E’s increases may be related to plant height; tiller number is inversely associated with HSPs expression, and chlorophyll content and C_i (intercellular CO₂ concentration) may be related to yield. Based on morphology, physiology, and gene regulation in heat and drought stress, we can discriminate genotypes that perform well under these stress conditions and utilize such genotypes as a source of genetic …