Eosinophilic chronic rhinosinusitis (ECRS) is characterized by the presence of nasal polyps, dominant ethmoid shadows in computed tomography (CT) scans, and elevated levels of eosinophil infiltration into the nasal polyps and peripheral blood. ECRS is often accompanied by severe asthma. The recent development of monoclonal antibody-based biologics, including benralizumab, has offered new therapeutic approaches for the treatment of asthma and allergic diseases. Asthma and ECRS are closely related; hence, benralizumab could provide clinical benefit in ECRS patients with severe asthma. Herein, we report a case of a 47-year-old female patient with severe asthma that presented with nasal obstruction and hearing impairment. Nasal endoscopic and otoscopic examinations indicated the presence of bilateral nasal polyps in the middle nasal meatus, as well as a bilateral effusion in the tympanic cavity. Sinus and temporal CT images showed dominant ethmoid sinus and tympanic cavity shadows. Biopsy of nasal polyps revealed high numbers of eosinophils, which led to the diagnosis of ECRS; eosinophilic otitis media (EOM) with hypereosinophilia was also suspected. Treatment with benralizumab reduced the number of peripheral blood eosinophils and improved asthma symptoms. Prolonged benralizumab administration also resulted in a remarkable size reduction in bilateral middle nasal polyps and aeration of the tympanic cavity. In conclusion, benralizumab treatment improved the symptoms of severe asthma, ECRS, and EOM. Eosinophil depletion could be an important mechanism by which benralizumab improves ECRS and EOM. The use of benralizumab for the treatment of ECRS and EOM patients with severe asthma merits further investigation in large-cohort studies.