Background Odontogenic sinusitis (ODS) is a common cause of unilateral sinus disease (USD), but can be challenging to diagnose due to nonspecific clinical presentations, potentially subtle to absent dental pathology on sinus computed tomography (CT), and underrepresentation in the sinusitis literature. Objective Identify sinonasal clinical variables predictive of ODS in patients presenting with unilateral maxillary sinus opacification on sinus CT. Methods A prospective cohort study was conducted on 131 consecutive patients with USD and at least partial or complete maxillary sinus opacification on sinus CT. Patients’ demographics, sinonasal symptoms (anterior and posterior drainage, nasal obstruction, facial pressure, smell loss, and foul smell), 22-item sinonasal outcome test, nasal endoscopy findings, CT findings, and histopathology were collected. Patients’ diagnoses included ODS, chronic rhinosinusitis with or without nasal polyps, and inverted papilloma. Demographic and clinical data were compared between patients with unilateral ODS and non-odontogenic disease using univariate and multivariate analyses. Results Of the 131 USD patients, 65 had ODS and 66 had non-odontogenic disease. The following variables were significantly associated with unilateral ODS on multivariate analysis: middle meatal pus on endoscopy (OR= 17.67, 95% CI-5.69, 54.87; p = 0.001), foul smell (OR= 6.11, 95% CI-1.64, 22.82; p=.007), facial pressure (OR= 3.55, 95% CI-1.25, 10.12; p = 0.018), and any frontal opacification on CT (OR= 5.19, 95% CI-1.68, 16.06; p = 0.004). Any sphenoid opacification on CT was inversely related to ODS (OR = 0.14, 95% CI-0.03, 0.69; p = 0.016). The study was adequately powered. Conclusion With unilateral maxillary sinus disease, the following features were significantly associated with ODS: foul smell, ipsilateral facial pressure, middle meatal pus on endoscopy, and any frontal sinus opacification on sinus CT. Additionally, any sphenoid sinus opacification on CT was inversely related to ODS. Presence or absence of these clinical variables can be used to increase or decrease one’s suspicion of an odontogenic source of sinusitis.