The aim of the study was to identify the chemical ingredients and to evaluate the antibacterial activity of crude extracts of locally grown Acacia karoo and Ziziphus mauritiana. Antibacterial activity was measured by the agar well diffusion method, and chemical ingredients were identified by gas chromatography-mass spectrometry. Qualitative analysis of crude organic extracts confirmed the presence of high-and low-molecular-mass compounds. The extracts had a broad spectrum of antibacterial activity. An ethyl acetate extract of A. karoo root induced a maximum zone of inhibition of Staphylococcus aureus (35 ± 1.15 mm) and the least activity against Proteus vulgaris (10 ± 1.52 mm). A methanol extract of Z. mauritiana root induced a maximum zone of inhibition of Escherichia coli (35 ± 1.15 mm) and had the least activity against Klebsiella pneumoniae (10 ± 1.52 mm). We conclude that root extracts of A. karoo and Z. mauritiana have significant antibacterial activity.