Acetone, Hexane, Ethylacetate and Acetone / Hexane / Ethylacetate (50/30/20 v/v/v) extracts of Vernonia amygdalina leaves (Del, belonging to the family Asteraceae) were investigated for antimicrobial activities. Three different concentrations (100 mg/mL, 50 mg/mL and 25 mg/mL) of each extract were used against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25920 and Candida albicans. The disc diffusion method was used. Phytochemical screening and High Performance Liquid Chromatography (HPLC) analysis of constituents of the extracts were also carried out. Highest yield (14.25 %) after extraction was obtained for acetone extract followed by hexane extract (8.2 %), Acetone/Hexane/Ethylacetate extract (7.4 %) and ethylacetate (7.1 %) extract. Tannin, steroids, saponin, terpenoid, flavonoid, anthraquinones were present in each of the solvent extracts. Coumarin was present in both acetone and Acetone/Hexane/Ethylacetate extracts while glycosides were present only in the Acetone/Hexane/Ethylacetate extract. Protein was present in ethylacetate extract and absent in the other solvent extracts. The extracts revealed dose-dependent activities against all the test organisms. Highest range of inhibition zone (15.00 mm- 18.00 mm) was obtained for Acetone/Hexane/Ethylacetate extract at 25 mg/mL against the test organisms while lowest range of inhibition zone (7.00 mm- 10.00 mm) was obtained for acetone extract at 100 mg/mL. Various compounds (Oxalate, Phyrate, Epivernodalol, Vernodalol, Venonioside A, Vernonioside B, Vernodalin, Luteolin, Andrographolide, Andrographoside) were separated at different peak heights (mV) and at varying retention times from all the solvent extracts. The solvent extracts of Vernonia amygdalina can serve as good alternative to orthodox medicine in the treatment of infections associated with the three test organisms.