Background: Podoconiosis is entirely preventable, non-communicable disease with high potential of elimination. The prevalence of podoconiosis in Ethiopia was 7.45%. One of the pillars for elimination of podoconiosis is morbidity control and management. Objective: the present study aimed to assess the knowledge, attitude, practices and associated factors of health professionals towards podoconiosis cause, prevention and treatments. Methods: Facility based cross-sectional study was conducted. The source population was all health professionals currently working in public health facilities. The final estimated sample size was 349. A pretested self-administrated structured questionnaire was used to collect the data. The data were coded, entered, and cleaned by using Epi.info version7, and analyzed by using SPSS version 20. Result: A total of 320 health professionals participated in the study. Sixty eight (23.1%) health professionals had poor knowledge towards podoconiosis. Seventy (21.9%) identified podoconiosis as infectious disease. Profession, address of health facility, service year and attitude of participants were significantly associated with knowledge towards podoconiosis. More than half (56%) had favorable attitude towards podoconiosis patients. Knowledge score (95%CI: 1.389, 4.059, p-value = 0.002) was the independent predictor for attitude status. Very few (11.6%) respondents treated podoconiosis patients. Age group 45 years old and above and training on lymphedema morbidity management and disability prevention were significantly associated with clinical experience in treating affected patients, (AOR = 17.345; 95%CI: 4.62, 65.119) and (AOR = 7.385; 95%CI: 2.5, 21.797), respectively. Conclusion: Despite, high percent of good knowledge of health professionals towards podoconiosis, clinical experience of health professionals in treating podoconiosis patients was very low. In-service trainings will be given for health professionals to improve treatment. In podoconiosis endemic districts hygiene supplies and other referencing materials should be made available for podoconiosis case management.