Pharyngitis is one of the most common diagnoses for antibiotic prescriptions worldwide. Antibiotics should be prescribed for bacterial pharyngitis to reduce its complications. The aims of this study were to assess antibiotic prescriptions for pharyngitis cases, and their relationship with physicians' knowledge regarding its diagnosis and management. A cross-sectional study was conducted. First, prescriptions for pharyngitis cases using the modified Centor criteria was evaluated at primary care centers in Saudi Arabia. Second, physicians' knowledge of the modified Centor score and the diagnosis and management of pharyngitis was assessed using a self-administered questionnaire. Out of 104 pharyngitis cases, 79% (n = 82) were prescribed antibiotics, of which 28% were evidence-based prescriptions. First-line antibiotics were prescribed in 34% of patients, and second-line (broad-spectrum) antibiotics such as amoxicillin/clavulanate were prescribed in half of the patients. The main significant predictors of antibiotic prescriptions were age < 3 years (odds ratio, 0.13; 95% CI, 0.02 to 0.97), tonsillar exudate (odds ratio, 21.14; 95% CI, 2.88 to 155.09), and throat erythema (odds ratio, 9.30; 95% CI, 1.18 to 73.41). Overall, physicians (n = 29) had adequate knowledge about the modified Centor score and the management of pharyngitis. Most prescribed antibiotics for pharyngitis were unnecessarily prescribed; the majority being broad-spectrum antibiotics. Despite physicians' adequate knowledge of the modified Centor score and the management of pharyngitis, their practice failed to demonstrate that. Induction of the Saudi Antimicrobial Stewardship Program in the primary care centers, accessibility to diagnostic tools, and educational programs may help in reducing unnecessary antibiotic prescriptions.