Some 3(2H)-pyridazinone and 1(2H)-phthalazinone derivatives were synthesized. The structures of these new compounds were confirmed by IR, (1)H-NMR, mass spectrum, and elemental analysis. The synthesized compounds were evaluated for their antibacterial activity against various gram-positive and gram-negative strains of bacteria and their clinical isolates and for their antimycobacterial activity against M. tuberculosis H37Rv. The results showed that the synthesized compounds were generally active against B. subtilis and its clinical isolate. Among the target compounds, compound 14c exhibited the best antibacterial activity, with a MIC value of 15.62 mu g/mL against B. subtilis. Compound 15e had the highest antimycobacterial activity.