Acute rheumatic fever (ARF) is a delayed autoimmune complication of Group A Streptococcal (GAS) pharyngitis and remains a significant public health concern in regions such as Saudi Arabia. Timely treatment with antibiotics guided by the Centor criteria can prevent ARF, yet adherence to these recommended guidelines remains inconsistent among physicians in developing countries. This study aimed to assess the knowledge and adherence of physicians in Jeddah, Saudi Arabia, to the Centor criteria in managing streptococcal pharyngitis as a strategy to prevent ARF. A cross-sectional study was conducted among 105 physicians across various specialties. A structured questionnaire was used to evaluate their adherence and awareness. Data was analyzed using SPSS version 23.0, with chi-square tests to assess the significance (P < 0.05). Only 40% of physicians reported consistent use of the Centor criteria. Female and non-Saudi physicians demonstrated higher rates of adherence. The most compliant were consultants (42.8%), while ENT and family medicine departments demonstrated better adherence to Ministry of Health guidelines. Additionally, physicians with over 15 years of experience demonstrated significantly greater adherence than their less experienced counterparts. Significant gaps were identified in the adherence to the Centor criteria, which were influenced by professional roles and demographic factors. Promoting adherence to national guidelines and standardizing training is crucial for improving ARF prevention in Saudi Arabia.