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Phytochemistry, antioxidant and antibacterial activities of different solvent extracts of Chromolaena odorata leaves obtained by direct and sequential extraction were compared in this study. Antibacterial evaluation of the extracts was performed through a disc diffusion method. The results revealed that the solvents, Petroleum ether and Ethyl acetate showed the presence of a majority of the phytochemicals, Chloroform extract yielded maximum TPC and TAA and ethyl acetate yielded higher TFC when compared to other solvents. Ethanol and chloroform extracts showed lower concentrations of IC50 against DPPH and NO radicals respectively. Acetone recorded the maximum zone of inhibition against Staphylococcus aureus and Pseudomonas aeruginosa; ethyl acetate against Bacillus subtilis and Chloroform against Streptococcus mutans. Among the solvents studied for phytochemical content and bioactivities, ethanol showed a higher level of phytochemical extraction and better bioactivities. As a direct solvent extraction of C. odorata showed better efficiency when compared with sequential extraction, the study strongly recommends the use of a direct extraction method.