The disease malaria is caused by a single-celled protozoan parasite species which belongs to the genus Plasmodium. There are five Plasmodium species that cause malaria in humans. These are P. falciparum, P. vivax, P. malaria, P. ovale, and P. knowlensi. It is one of the major human diseases that contribute significantly to morbidity and mortality around the world. Although there is a significant burden of malaria in Ethiopia, including the present study area, little is known about its epidemiology and associated risk factors. The study was set out to assess the prevalence of malaria and its associated risk factors among patients attending Fenote Selam General Hospital, Northwest Ethiopia. A hospital based cross-sectional study was conducted at Finote Selam General Hospital, during April-May, 2022. A pretested and structured questionnaire survey was carried out to obtain the socio-demographic and other explanatory variables among the study participants. A total of 424 randomly selected individuals participated in the questionnaire survey and blood sample collection. The prevalence of malaria was calculated using descriptive statistics. Bivariate logistic regression analysis was used to assess the associations between independent and dependent variables. Those significant variables by bivariate regression were selected for multivariate logistic regression analysis using a backward elimination method to avoid the cofounding effect. The differences were considered to be statistically significant if the value was less than 0.05. From a total of 424 blood samples examined, 93 (21.9%) samples were found positive for malaria parasite infection. Of all malaria cases, 69.9%, 23.7%, and 6.5% were P. falciparum, P. vivax, and mixed infections, respectively. In the current study area, age group less than 5 (AOR = 2.377; 95% CI: 1.652, 4.149), rural residence (AOR = 4.175; 95% CI: 1.404, 12.409), presence of stagnant water near home (AOR = 4.52; 95% CI: 2.323, 8.733), experience of outdoor activity during the night (AOR = 7.012; 95% CI: 6.990, 14.412), wearing long clothes during the night (AOR = 3.91; 95% CI = 2.904, 7.285), and ITN using status (AOR = 4.39; 95% CI = 2.34, 7.85) were associated with malaria parasite infection in the present study area. The current findings showed that malaria remains a serious public health problem in the study area. Therefore, further efforts are needed to monitor and evaluate the effectiveness of control measures in order to eradicate and control malaria in the study area.