Coffee is a popular beverage owing to its unique flavor and diverse health benefits. The current study aimed at investigating the antioxidant activity, in relation to the phytochemical composition, of authenticated Brazilian green and roasted Coffea arabica and C. robusta, along with 15 commercial specimens collected from the Middle East. Ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-ESI–HRMS) and UV spectrometry were employed for profiling and fingerprinting, respectively. With the aid of global natural product social molecular networking (GNPS), a total of 88 peaks were annotated as belonging to different chemical classes, of which 11 metabolites are reported for the first time in coffee seeds. Moreover, chemometric tools showed comparable results between both platforms, with more advantages for UV in the annotation of roasting products, suggesting that UV can serve as a discriminative tool. Additionally, antioxidant assays coupled with the UHPLC-ESI–HRMS dataset using partial least-squares discriminant analysis (PLS-DA) demonstrated that caffeoylquinic acid and caffeine were potential antioxidant markers in unroasted coffee versus dicaffeoyl quinolactone and melanoidins in roasted coffee. The study presents a multiplex metabolomics approach to the quality control of coffee, one of the most consumed beverages.