Article InfoStress is a state of an individual that result from the interaction of the individual with the environment which is perceived as threatening or threat to the well-being. University students encounter a great deal of academic, personal and social stress during their academic activities. The purpose of the present study was to assess the effect of stress and associated factors on academic achievement among Ambo University students. Mixed method explanatory design was conducted on a sample of 343 students at Ambo University. Data were collected using the Student-life Stress Inventory. Descriptive statistics, independent t-test, ANOVA and Pearson correlation coefficient were utilized to analyze the collected data using SPSS version 20. As a result, the general life time prevalence of stress was 24.5%. More specifically, fear of academic failure, fear of family disappointment, lack of motivation and interpersonal relationship problem were highly reported symptom of stress students. Likewise, academic overload, assignments timings, political situation of country, financial strain, high family expectations, study skill problem, being alone, procrastination, living away from home, difficulty reading materials, language barrier, acculturation, relationship with opposite sex, lack of entertainment in the University, lack of family support, time management problem, and lack of personal interest in their department were frequently reported causes of stress in the University respectively. In this study, the independent t-test result shows that there was a statistically significant mean difference in experiencing stress across students' sex and residential area. Besides, ANOVA result revealed that year of study, students' perceived social support and perceived parenting style of the respondents had a significant effect on stress. Also, a statistically significant negative and moderate relationship was reported between stress and academic achievement. To sum up, nearly one fourth of students were suffering from measureable stress. Therefore, Ambo University management shall strengthen the academic counseling and preventive mental health services for the students so as to provide a conducive learning environment.