The aim of the present study was to examine the impact of stress and coping on substance abusernamong Debreberhan University students. A cross sectional survey research design usingrnquantitative research approach was employed in this study. Stratified random sampling was usedrnto select 364 ( 220 male and 144 female) participants from the target population after stratifyingrnby colleges, department and sex. Data were gathered through self-administered questionnaire.rnData obtained were analyzed using descriptive statistics, T- tests, analysis of variance (ANOVA)rnand regression. Results of the study showed that, lifetime prevalence rates of Tobacco was 19.6%rn, alcohol 62.7%, cannabis 9.8%, and Chat/Khat 25.4% while current prevalence rates forrntobacco, alcohol, cannabis and chat were14.7%, 44.2%, 5.5%, and 22.3% respectively. Thernresults of Regression analysis has shown that both stress and coping significantly predictrnsubstance abuse, with stress and disengagement coping yielding unique contribution for therndependent variable. The results of the T- test has also shown that there were significant genderrndifferences in the mean scores of stress, coping and substance abuse among participants. Fromrnthis study the magnitude of substance abuse is high. Stress and disengagement coping are thernfactors that have contributed to students substance abuse. Thus, there is a need to increasernpublic awareness of the potential impacts of substance abuse, specially adolescents, and alsornhelp them identify effective and healthy coping strategies to forestall the onset of substance use