The purpose of this study was to examine the extent to which transgender people have observed negative transgender-related messages in the media and the relationship between negative media message exposure and the mental health of transgender people. In 2019, 545 transgender adults completed an online survey assessing demographics, negative transgender-related media messages, violence, and mental health. Separate multivariable logistic regression models examined the association of frequency of negative media exposure and clinically significant symptoms of depression, anxiety, post-traumatic stress disorder (PTSD), and global psychological distress. Mean age of the sample was 31.2 years (standard deviation [SD] = 11.2). Nearly half identified as nonbinary (42.2%), 82.0% were White, non-Hispanic, 56.9% had a college degree, and 67.0% were financially insecure. The majority reported experiencing childhood abuse (60.6%) and abuse in adulthood (58.0%). The mean frequency of exposure to negative transgender-related media was 6.41 (SD = 2.9) with 97.6% of the sample reporting exposure to negative media depictions of transgender people across a range of mediums. In separate multivariable models adjusted for age, gender identity, race, education, income, and childhood/adult abuse, more frequent exposure to negative depictions of transgender people in the media was significantly associated with clinically significant symptoms of depression (adjusted odds ratio [aOR] = 1.18; 95% confidence interval [CI] = 1.08-1.29;  = 0.0003); anxiety (aOR = 1.26; 95% CI = 1.14-1.40;  < 0.0001); PTSD (aOR = 1.25; 95% CI = 1.16-1.34;  < 0.0001); and global psychological distress (aOR = 1.28; 95% CI = 1.15-1.42;  < 0.0001). Exposure to negative media messages from multiple sources necessitates multilevel interventions to improve the mental health of transgender people and curb stigma at its source.