The burden of mental disorders continues to grow with significant impacts on health. This study aimed to investigate the prevalence of stress, anxiety, and depression in Yazd adult population and to examine the associated socioeconomic factors. In a 2-step cluster sampling process, 10 000 residents of Yazd Greater Area (200 clusters of 50) were selected during 2014-2015. The short version of Depression, Anxiety and Stress Scale (DASS) Questionnaire was used to assess relevant depression, anxiety, and stress. Data were analyzed by chi-square test. All statistical analyses were done using SPSS version 16.0. P-values less than 0.05 were considered statistically significant. Depression, anxiety, and stress were seen in 29%, 32.2%, and 34.8% of adult residents of Yazd Greater Area, respectively. The symptoms of the disorders were moderate, severe, and very severe in 18.2%, 20.2%, and 23.4% of the population, respectively. Also, a significant difference was found between the symptoms of depression, anxiety, and stress and sex, age group, education, employment, marriage status, and country of birth. Of the total population under study, 3.7% were depressed, 7.7% were anxious, 9.5% had stress alone and 16.4% had symptoms of all the 3 disorders. Frequency of depression among Zoroastrians was more than muslims (42.1% vs 29.7%). Despite achievemments in higher education and economic development of Yazd population over the past 2 decades, the trend of these disorders has alarmingly been increased. Considering the findings, it is necessary to develop evidence-based and appropriate community-based primary and secondary mental health prevention programs.