Background: Chronic otitis media (COM) is a chronic inflammatory disease of the middle ear and mastoid. This study has shown the current patterns of antimicrobial sensitivity and resistance of the commonly prescribed antimicrobials in patients with COM (squamosal), of our catchment area, visiting the ear, nose, and throat outpatient department (ENT OPD). Methods: Observational cross-sectional study—a total of 332 patients with a chronically discharging ear presented to the ENT OPD during the study period, and among these patients, 34 cases diagnosed as squamosal COM were taken for this study. Ear discharge was sent for culture and sensitivity testing, and processed immediately in the laboratory. Role of antimicrobials in squamosal COM—although the primary modality for treatment is surgical/mastoid exploration, knowledge of the antimicrobial sensitivity patterns helps in prescribing postoperative antibiotics (when required) and also helps in countering the emergence of “resistant strains” due to empirical therapy in such cases. Results: In squamosal COM, the most common organisms were in the order Staphylococcus aureus followed by Pseudomonas aeruginosa, Kelbsiella, and Proteus mirabalis. • Staphylococcus aureus: The antibiotics showing maximum sensitivity were piperacillin + tazobactam, almost equally with imipenem or meropenem, and followed by azithromycin. • Pseudomonas aeruginosa: Most sensitive for piperacillin + tazobactam followed by fourth-generation cephalosporins. Ciprofloxacin was also found to show intermediate sensitivity. • Klebsiella: Most sensitive for second-generation cephalosporins followed almost equally by piperacillin + tazobactam and levofloxacin. Conclusion: Analysis of the antibiotic susceptibility revealed that the penicillin group of antibiotics showed tremendous resistance. Resistance has also been shown toward older macrolide antibiotics such as azithromycin. Cephalosporin antibiotics have shown good sensitivity but resistance has emerged against these as well, which could be attributed to their indiscriminate usage in recent times. Newer antibiotics such as imipenem and meropenem and piperacillin + tazobactam have shown excellent sensitivity in this study. We recommend their judicious use to prevent resistance.