Abstract: Background and Objectives: Cassia siamea widely distributed in the southern and northern parts of Nigeria is extensively used in folkloric medicine for the treatment of urinogenitory disorders, herpes, rhinitis, constipation, diabetes, insomnia, hypertension, asthma, typhoid fever, microbial infections among others. The study was aimed to screen the antimicrobial potency of the methanol stem bark extract of C. siamea as well established the phytoconstituents responsible for such activity. Materials and Methods: This study was evaluated the phytochemistry, antimicrobial effects as well as the GC-MS analysis of Cassia siamea stem bark extracted with absolute methanol using cold maceration method for 72 h. Results: The extract showed promising antibacterial activity against all the tested pathogens namely Streptococcus pyogenes, Staphylococcus aureus, Klebsiella pneumoneae, Salmonella typhi, Shigella sp, Escherichia coli and Pseudomonas aeruginosa. The best activity was recorded for the gram negative strain of E. coli with a zone of inhibition (mm) of 16.77±0.22 while the least activity was recorded for the gram positive strain of S. aureus with a zone of inhibition (mm) of (11.16±0.12) at the highest investigated concentration of 100 mg mL–1. The GC-MS analysis confirmed the occurrence of a total 23 phytocompounds in the methanol extract. Conclusion: The stem bark extract has varying degree of antimicrobial potential ranging from mild to high activity correlated by the presence of selected bioactive compounds.