A series of new substituted benzamides were synthesized and tested in vitro for their antibacterial activity against Gram-positive and Gram-negative bacteria and as well for antifungal activity. The compounds 8i and 9 showed better activity among the different benzamides synthesized. The structural characteristics governing antibacterial activities of substituted benzamides were studied using QSAR methodology. The results showed that the antimicrobial activity could be modeled using the topological descriptors, molecular connectivity indices (2chi(v) and 2chi) and Kiers shape index (kappaalpha1). The low residual activity and high cross-validated r2 values (r(cv)2) observed indicated the predictive ability of the developed QSAR models.