Objective This study assessed the unique coping strategies of transgender and gender nonconforming (TGNC) individuals in the United States used to manage gender‐related stress, and examined associations between specific coping profiles and mental health. Methods Data were from 316 participants in the 2014–2015 Transgender Stress and Health Study, an online study of TGNC mental and sexual health. A factor analysis of the coping measure (Brief COPE) was followed by a k‐means cluster analysis to evaluate distinct profiles of coping with gender‐related stress. Proportional odds models and logistic regression models indicated how coping profiles related to levels of self‐reported depressive symptoms and suicidality. Results A 4‐factor structure was identified with three distinct profiles of coping with gender‐related stress, each representative of the frequency (high or low) in which participants used functional and dysfunctional coping strategies: (a) high‐functional/low‐dysfunctional, (b) high‐functional/high‐dysfunctional, and (c) low‐functional/low‐dysfunctional. There were significant differences in depressive symptoms and suicidality based on distinct gender‐related coping profiles. The high‐functional/high‐dysfunctional group reported significantly poorer mental health compared with the high‐functional/low‐dysfunctional group. Conclusion To improve mental health outcomes in TGNC individuals, health providers and researchers should strive to not only promote functional coping strategies for managing gender‐related stress but also decrease dysfunctional coping strategies.