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Introduction: Curriculum-based sexual and reproductive health education (CBSRHE) is one of the preventive strategies targeting youth in higher institutions to protect them from sexual and reproductive health problems, despite never assessing the effect in Ethiopia. Therefore, this study aimed to assess the effect of CBSRHE on knowledge and attitude about SRH services to have safer sexual behaviors among first-year students of Arba Minch University., Method: We conducted a quasi-experimental study among purposively selected campuses. The campuses were allocated to (i) an intervention arm consisting of curriculum-based sexual and reproductive health, or (ii) a control arm for those who were free from intervention. Data was collected, at baseline and immediately after the intervention ended by using a structured self-administered questionnaire. To compare differences in the change from baseline to post-intervention between the two arms we use the chi-square test and independent-samples t-test. To see the effect of the CBSRHE by controlling the effect confounding inverse probability-weighted analysis was conducted., Result: A total of 832 and 820 students participated in a baseline and post-test respectively. The proportion of youth who practice receptive penetrative sex decreases from 40.9% to 28.3% in the intervention arm compared to 37.6% to 37.3% in the non-intervention arm between baseline and end line, with statistically significant differences between groups. However, there are statistically significant differences between the intervention and control groups in terms of changes in contraception utilization (X2 = 1.21; P>0.05). Furthermore, there were significant improvements in knowledge and attitude among the intervention arm a comprehensive knowledge of HIV/AIDS (ATE = 0.22,95% CI, 0.14 to 0.29; p < 0.01), an average change of attitude toward HIV/AIDS(ATE = 1.32, 95% CI, 1.18 to 1.47; p < 0.01), comprehensive condom knowledge score (ATE = 0.23, 95% CI, 0.13 to 0.33; p < 0.01) and the average change of attitude toward condom score (ATE = 1.83, 95% CI, 1.19 to 2.77; p < 0.01)., Conclusion and Recommendation: It was found that there was a significant difference in knowledge and attitude toward a disk sexual behaviors among r one student. This implies that the educational authority o the country can gain through the adoption of courses to all universities across the country, besides doing further comparative studies to determine the long-term effect of the course supported with models and/or theories like the theory of change., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Boti Sidamo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)