This study evaluated the dimensionality, invariance, and reliability of the Depression, Anxiety, and Stress Scale-21 (DASS-21) within and across Brazil, Canada, Hong Kong, Romania, Taiwan, Turkey, United Arab Emirates, and the United States (N = 2,580) in college student samples. We used confirmatory factor analyses to compare the fit of four different factor structures of the DASS-21: a unidimensional model, a three-correlated-factors model, a higher order model, and a bifactor model. The bifactor model, with three specific factors (depression, anxiety, and stress) and one general factor (general distress), presented the best fit within each country. We also calculated ancillary bifactor indices of model-based dimensionality of the DASS-21 and model-based reliability to further examine the validity of the composite total and subscale scores and the use of unidimensional modeling. Results suggested the DASS-21 can be used as a unidimensional scale. Finally, measurement invariance of the best fitting model was tested across countries indicating configural invariance. The traditional three-correlated-factors model presented scalar invariance across Canada, Hong Kong, Romania, Taiwan, and the United States. Overall, these analyses indicate that the DASS-21 would best be used as a general score of distress rather than three separate factors of depression, anxiety, and stress, in the countries studied.