Parthenium hysterophorus is a weed of global concern with high threshold of tolerance against most of biotic and abiotic stresses. Phytochemical profile and in vitro antioxidant analysis may help in understanding its tolerance to stresses. Root, stem, leaf, phyllary, and receptacle (including disc and ray florets) were chemotyped employing GC tof-MS and assessed for antioxidant activity by DPPH, FRAP, HRSA, and TAC assays. Phytochemicals identified were terpenes, fatty acids, hydrocarbons, phytosterols, and compounds of miscellaneous chemical nature. Organ-specific maximum concentration of metabolite was β-vatirenene (root), hexadecanoic acid methylester (stem), aristolene epoxide (leaf), hexadecanoic acid methylester (phyllary), and hexadecanoic acid methylester (receptacle). Identified metabolites could be associated with stress tolerance mechanisms, basic metabolism, and allelopathy, etc. Root extracts showed highest antioxidant potential followed by receptacle. It can be concluded that diverse and unique phytochemical profile and great antioxidant potential make P. hysterophorus stress-tolerant, hence a weed of global habitat.