Background: Mpox is a rare but re-emerging zoonotic disease that causes significant morbidity and mortality. As primary care physicians serve as gatekeepers in the healthcare system, it is essential that they be proficient at identifying and coordinating care for suspected mpox patients. However, there is a scarcity of studies on the knowledge of mpox among primary care doctors in the northwestern geopolitical zone of Nigeria. Objectives: This study assessed the knowledge of mpox and its associated sociodemographic factors among primary care physicians in northwestern Nigeria. Methods: This online survey involved 155 primary care physicians practicing in seven northwestern states of Nigeria. Results: The questionnaire completion rate was 91.2% (155/170). The mean age of participants was 38.8±7.4 years, with male preponderance (60.7%). Most were general outpatient clinic doctors (77.4%), with ≥10 years of practice experience (63.2%), and senior registrars (36.1%). Only 18.9% had prior experience in diagnosing or managing mpox. Nine (5.8%) had good knowledge of mpox, with a mean overall knowledge score of 61.7±12.5%. Participants with ≥10 years of practice experience (p=0.049), senior professional cadres (p=0.031), and involvement in diagnosing or managing mpox (p=0.021) were associated with higher mean knowledge scores. Conclusions: The overall knowledge rate was notably low, indicating significant gaps in participants’ knowledge of the various aspects of the disease. Senior professional cadres, long practice years, and experience in the diagnosis and management of mpox were associated with higher yet suboptimal knowledge scores. Hence, targeted educational interventions are needed to enhance their preparedness to identify and coordinate mpox cases in primary care settings.