Abstract: Background and Objective: Bacterial, fungal, parasitic and viral infections are still a major threat to public health. The impact is particularly alarming in developing countries due to the relative unavailability of medicines and the emergence of widespread drug resistance. This has lead to the search of new antimicrobial agents mainly among plant extracts. The aim of this research was to isolate, purify and test for antibacterial activity of compounds isolated from the stem bark extract of Sclerocarya birrea (A. Rich, Hochst.). Materials and Methods: Crude methanolic extract was partitioned into solvent of varied polarity. The resulting fractions were taken for bioactivity (antibacterial) test. The most active fraction was then subjected to isolation and purification techniques. Isolation and purification were carried out using thin layer and column chromatographic techniques. The bioactivity (antibacterial) test was done using agar well diffusion method, while MIC and MBC were tested using broth dilution method. Results: About 4 compounds/fractions were obtained after successive thin layer and column chromatography of ethyl acetate fraction. Only compound/fraction 2 showed remarkable antibacterial activity. It showed high zone of inhibition, MIC and MBC against most of the bacterial isolates. It was found to inhibit the growth of most of the test bacterial isolates comprising of both Gram-positive and Gram-negative organisms. On the other hand, the other fractions showed little or no activity against most of the test isolates. Conclusion: The result of the present study signifies the potential of Sclerocarya birrea stem bark as a source of therapeutic agents, which may provide leads in the ongoing search for anti-microbial agents from plants.