Background: Schistosomiasis is one of the most prevalent parasitic diseases and an important public health problem in many developing countries including Ethiopia. This study assessed prevalence of Schistosoma mansoni infection and associated factors among students attending elementary schools in Wondo Genet District ,Southern Ethiopia. Method: A quantitative school based cross-sectional study was carried out on a sample of 477 students. First, all elementary schools in Wondo Genet District were stratified based on their agro-ecology. Then, five and two schools were randomly selected from Midland (Woyina Dega) and Highland (Dega), respectively from each stratum. The sample size was proportionally allocated according to the total number of students in each school. Finally, systematic sampling technique was used to draw study participants by using a sampling interval (k-value) of calculated as 6735/492 =14. The sampling frame was made by listing all students based on the enrollment list of each school. A pre-tested structured questionnaire was used to collect data on socio demographic characteristics, knowledge on preventive and control of Schistosomiasis ,water contact behavior, hygiene and sanitation. Stool examination was done to determine prevalence of Schistosomiasis. The analysis was carried out using epi-info version 7 and SPSS version 20. Finally, logistic regression was used to determine the factors affecting Schistosoma mansoni infection. Results: The overall prevalence of S.mansoni infection was 16.4%(95% CI:13.4,19.7). Children in the age range of 5-9 years were 64%, AOR=0.36(95% CI:0.17,0.59) and those 10-14 years old were 95%, AOR=0.05(95% CI:0.01,0.35) less likely to be infected by S.mansoni compared to those 15-19 years old. Those who do have poor knowledge on preventive and control methods of S.mansoni, AOR=3.88(95%CI:2.25,11.76),respondents who do not wear shoes, AOR=4.23(95% CI:3.95,8.26) were at increased risk of being infected by S.mansoni. Students who do not wash clothes in streams, AOR=0.19(95% CI:0.08,0.23) had 81% reduced risk of S.mansoni infection than those who wash clothes in the streams. Conclusion and recommendations: The prevalence of S. mansoni was high in the study area. Age, poor knowledge level, washing clothes in streams and do not wearing shoes were significantly associated with occurrence of S.mansoni infection. Therefore, awareness creation at schools and mass drug administration is recommended.