Adolescents from minority groups are particularly susceptible to poor oral hygiene behaviors, including lack of daily flossing. This cross-sectional study aimed to conduct an exploratory behavioral research to identify evidence-based (theory-based) approaches to promote flossing behavior among African American/Black and Latinx/Hispanic (minority) adolescents. A 39-item psychometrically valid web-based questionnaire was used to collect responses from a nationwide sample of minority adolescents aged 10-17 years residing in the United States. The data were analyzed using bivariate and multivariate statistical methods. Of 520 minority adolescents (260 African American/Black and 260 Latinx/Hispanic adolescents), the proportion of flossing was nearly equally split in the sample. A significantly higher proportion of minority adolescents who were flossing had access to floss as opposed to those who were not flossing (86.8% vs. 69.8%, p < 0.001). A significantly higher proportion of minority adolescents who were not flossing did not visit the dentist over the past year as opposed to those who floss (25.2% vs. 14.7%, p < 0.001). Among the participants who were not flossing, gender, grade level, instruction in school regarding flossing, and multi-theory model (MTM) of health behavior change constructs were the significant predictors (p < 0.001) of initiating and sustaining flossing. The findings of this study will serve as baseline data for developing and evaluating effective evidence-based interventions using the MTM.