Secondary metabolites constitute an important group of plant-derived compounds with diverse biological activities and potential applications in phytomedicine. This study comparatively evaluated the secondary metabolite profiles and Fourier Transform Infrared (FTIR)-based chemical fingerprints of three Vernonia species (Vernonia amygdalina, Vernonia conferta and Vernonia volkamerifolia) occurring in Nigeria. Leaf extracts were fractionated using hexane, ethyl acetate and ethanol solvents. Qualitative phytochemical screening was conducted using standard phytochemical procedures, while quantitative metabolite determination was carried out using established analytical methods. Data were analyzed using one-way ANOVA at p < 0.05, and FTIR spectroscopy was used to characterize the chemical fingerprints of the extracts. The results revealed the occurrence of alkaloids, flavonoids, saponins, tannins, anthraquinones, terpenoids, cardiac glycosides, phenols and steroids, although their distribution varied among species and solvent fractions. Quantitative analysis showed significant interspecific variation (p < 0.05) in metabolite concentrations, with V. amygdalina exhibiting the highest flavonoid content (5.22 ± 0.172%), while V. conferta recorded higher concentrations of alkaloids (1.90 ± 0.100%) and saponins (1.85 ± 0.150%). Ethyl acetate and ethanol fractions generally yielded greater metabolite recovery than the hexane fraction, highlighting the influence of solvent polarity on extraction efficiency. FTIR analysis of the ethyl acetate fractions revealed characteristic absorption bands corresponding to functional groups such as C–H, C=O, C=C, C–O and N–H, indicating the presence of diverse classes of bioactive metabolites, including phenolics and flavonoids. The observed differences in metabolite composition and FTIR fingerprints among the three species demonstrate interspecific chemical variability within the genus Vernonia and provide baseline information for plant metabolite characterisation, chemotaxonomic studies, and future pharmacological investigations.