Background: Epilepsy, defined as seizure activity that is recurrent, unpredictable, and typically unprovoked. It is one of the most common disorders of the nervous system. Sociocultural attitudes in many African nations continue to have a negative impact on epilepsy management. It has been found that stigma and discrimination against people with epilepsy are more devastating and harmful than the illness itself. This is mainly attributed to misconceptions about the disease with fear and fright of the public on confronting an epileptic seizure. So, the current study assesses the community's attitude toward epilepsy patients and associated factors towards epilepsy in South Achefer District, Northwest Ethiopia. Methods: Community-based cross-sectional study triangulated with the qualitative method was conducted from March 1 to May 30, 2020 in South Achefer District. A systematic sampling technique was used to select a total of 762 individuals. Data were collected by faceto-face interview using a structured questionnaire and analyzed using SPSS version 23. Logistic regression analysis was performed and P < 0.05 with a 95% confidence interval was considered to measure statistically significant variables. For the qualitative study participants were selected purposively. Focus Group Discussion, key Informant Interview, and Individual Depth Interview were conducted until it reaches the point of saturation. Thematic analysis was done by using an open code software version 4.2. Results: A total of 753 respondents participated which gave a 98.8% response rate. Among those 60.8% (95% CI: 57.2-64.3) were found to have a favorable attitude towards epilepsy patients. Being informed about epilepsy (AOR=1.47; 95% CI, 1.02-2.11), witnessing seizure in the past (AOR=1.6; 95% CI, 1.14-2.27), and having good knowledge about epilepsy (AOR=2.08; CI, 1.49-2.89) were the variables that showed statistically significant association with a favorable attitude. Conclusion: The favorable attitude of the community towards epilepsy patients was found high in the study area. Information about epilepsy, witnessing seizure, and knowledge about epilepsy showed a significant association with attitude. Therefore, health professional and health extension workers should provide a larger and comprehensive community-based education to enhance people's knowledge about epilepsy to bring attitude change against a negative attitude towards epilepsy.