A series of simple heterocyclic chalcone analogues have been synthesized by Claisen Schmidt condensation reactions between substituted benzaldehydes and heteroaryl methyl ketones and evaluated for their antibacterial activity. The structures of the synthesized chalcones were established by IR and ¹H-NMR analysis. The biological data shows that compounds <strong>p₅</strong>, <strong>f₆</strong> and <strong>t₅</strong> had strong activities against both susceptible and resistant <em>Staphylococcus aureus </em>strains, but not activity against a vancomycin and methicillin resistant <em>Staphylococcus aureus</em> isolated from a human sample. The structure and activity relationships confirmed that compounds <strong>f₅</strong>, <strong>f₆</strong> and <strong>t₅</strong> are potential candidates for future drug discovery and development.