Examinations of the internal structure of the Depression, Anxiety, and Stress Scale-21 (DASS-21) have yielded inconsistent conclusions within and across cultural contexts. This study examined the dimensionality and reliability of the DASS-21 across three theoretically plausible factor structures (i.e., unidimensional, oblique three-factor, and bifactor) as well as measurement equivalence/invariance of the DASS-21 using two different approaches (i.e., multigroup confirmatory factor analysis and the alignment approach) with a large, diverse sample of 2,920 young adult college student participants from nine countries/regions (i.e., Australia, Brazil, Germany, Hong Kong, Lithuania, Taiwan, Türkiye, United Arab Emirates, and the United States). Results showed an excellent fit of the bifactor model in all countries/regions except the UAE and the US in which the model did not converge. Regarding parameter equivalence, we found configural, threshold, and loading invariance for the oblique three-factor model (across the nine studied countries/regions) and for the bifactor model (across seven countries/regions). Results indicate that DASS-21 scores measure a general psychological distress factor with more validity and reliability than depression, anxiety, or stress constructs independently. Findings supported the bifactor structure of DASS-21 and demonstrated that cross-cultural comparisons using this scale should be conducted using proper procedures, such as the alignment approach.