Inflammation is a key pathological process underlying numerous acute and chronic disorders, and while non-steroidal anti-inflammatory drugs (NSAIDs) remain widely prescribed, their clinical utility is restricted due to adverse effects such as gastrointestinal bleeding, hepatotoxicity, and the emergence of resistance during prolonged therapy. To overcome these limitations, heterocyclic scaffolds have emerged as privileged structures in medicinal chemistry, with benzimidazole and oxadiazole derivatives showing strong potential as anti-inflammatory agents. In the present study, a series of benzofused nitrogen-containing heterocyclic derivatives were designed and synthesized by employing 2-mercaptobenzimidazole as the core pharmacophore. The synthetic pathway involved the initial formation of thioacetate from 2-mercaptobenzimidazole and ethyl-2-chloroacetate in ethanolic KOH, followed by hydrazinolysis to yield the corresponding acetohydrazide, which was subsequently cyclized with various substituted aromatic acids in the presence of H₂SO₄ to afford the final heterocyclic derivatives. Structural elucidation was achieved using FT-IR, ¹H-NMR, and mass spectrometry, where spectral data confirmed the disappearance of primary amine/amide peaks and the appearance of diagnostic C=N, C–O–C, and secondary amine signals. Proton NMR spectra revealed characteristic –CH₃/–CH₂ resonances (1.0–4.0 ppm) and aromatic signals (7.0–9.0 ppm), while molecular ion peaks (M+1) in mass spectra validated the expected molecular weights. Toxicological evaluation using AOT 425 guidelines established an LD₅₀ of 1103 mg/kg, suggesting an acceptable safety margin. Pharmacological screening via carrageenan-induced rat paw edema assay demonstrated that the synthesized compounds, administered at 110 and 130 mg/kg, produced significant inhibition of inflammation, comparable to standard reference drugs. Overall, the findings highlight the promising anti-inflammatory potential of the synthesized benzofused heterocycles and support further optimization for drug development