Background: Vernonia amygdalina (Del.) has been reported to have medicinal values, and the phytochemical constituents which is present in different parts of the plant have been found to be responsible for the antimicrobial efficacy of the plant. This study focuses on the antibacterial activity of the stem bark extracts of V. amygdalina against Multiple Antibiotic-Resistant (MAR) bacteria isolated from wound samples and also characterize the bioactive compounds present in the plant. Methods: Bacteria were isolated from wound samples using standard microbiological techniques and disc diffusion method was used to determine the sensitivity patterns of the isolated bacteria to conventional antibiotics and to the various extracts of V. amygdalina stem bark. Ciprofloxacin was used as control during the antibacterial assay. GC-MS analysis was carried out to identify the bioactive compounds in the stem bark extracts of the plant. Results: Pseudomonas aeruginosa (36%), Staphylococcus aureus (29%), Staphylococcus epidermidis (14%), Bacillus subtilis (6%), Escherichia coli (6%), Klebsiella pneumoniae (5%), and Proteus mirabilis (4%) were the bacteria isolated from the wound swabs sampled in this study. The ethyl acetate extract of V. amygdalina (300mg/ml) inhibited the growth of these organisms with the greatest effect on S. aureus with inhibition zone of 23.17±0.60 mm. The GC-MS analysis of the plant extracts revealed the presence of bioactive compounds such as coumarin, oleic acid, among others. Conclusion: The findings from this study have further established that V. amygdalina is a promising candidate and effective alternative treatment means for MAR bacteria that are associated with wound infections.