Abstract Introduction Pain is the most frequent presenting complaint in patients consulting or admitted to the emergency department (ED). Thus, its acute management is often done by physicians working in the ED. These clinicians are often general practitioners and not emergency medicine physicians in resource-poor settings. Hence, a mastery of pain management by these physicians may be important in relieving acute pain. We aimed to assess the knowledge, to determine the attitudes and practices of physicians in the management of pain in EDs of Cameroon. Methods We carried out a prospective cross-sectional study over 4 months in the year 2018. We enrolled all consenting physicians who were neither emergency medicine doctors nor anesthesiologists working at the EDs of five tertiary hospitals of Cameroon. Using a validated and pretested structured questionnaire, data on the knowledge, attitudes, and practices of acute pain management at the ED by these clinicians were studied. We used an externally validated score to assess the knowledge as either poor, insufficient, moderate or good. Results A total of 58 physicians were included; 18 interns or residents and 39 general practitioners. Their mean age was 28.6 ± 3 years and their average number of years of practice was 2.9 years. The level of knowledge was rated “poor” in 77.6% of physicians. Being a general practitioner was significantly associated with a poor level of knowledge (p = 0.02; OR = 5.1). We found a negative and significant correlation between knowledge and years of practice (p = 0.04; r2 = 0.06). More than three-quarter (82.8%) of participants used a pain scale to evaluate the severity of pain. The most used scale was the Visual Analog Scale (56.9%). The most frequently used analgesic was paracetamol (98.3%), although only 3.5% of physicians correctly knew its half-life, delay of onset of action and duration of action. Conclusion These findings suggest that physicians in EDs of Cameroon have poor knowledge and suboptimal practices in pain management. General practice and a greater number of professional experience seemed to favour these attitudes. Overall, there is an urgent need for refresher courses in acute pain management for physicians working in these resource-limited EDs.