Objective: To remedy the notable gap in evidence-based treatments for sexual minority women, this study tested the efficacy of a minority-stress-focused cognitive-behavioral treatment intended to improve this population's mental and behavioral health. Method: The intervention, EQuIP (Empowering Queer Identities in Psychotherapy), was adapted from a transdiagnostic cognitive-behavioral treatment as also recently adapted for sexual minority men. Sexual minority women at risk of mental and behavioral health problems (n = 19) and expert providers with this population (n = 12) shaped the treatment's development, including by supporting its primary focus on universal and minority-stress-focused processes underlying this population's disproportionately poor mental and behavioral health. The resulting treatment was then delivered to young adult sexual minority women (n = 60; M age = 25.58; 41.67% racial/ethnic minority; 43.33% transgender/nonbinary) experiencing depression/anxiety and past 90-day heavy alcohol use. Results: Compared to waitlist (n = 30), participants randomized to immediately receive EQuIP (n = 30) experienced significantly reduced depression and anxiety (d = 0.85, 0.86, respectively); effects for alcohol use problems were smaller (d = 0.29) and marginally significant. In pre- to post-intervention pooled analyses, effect sizes for minority stress processes (mean d = .25) and universal risk factors (mean d = .48), through which the treatment was expected to work, were small and moderate, respectively, and in the expected direction. Conclusions: This study provides initial support for a minority-stress-focused transdiagnostic cognitive-behavioral treatment for sexual minority women. These first results can launch exploration of other mechanisms and modalities through which to equip this population with evidence-based support. What is the public health significance of this article? Sexual minority women represent one of the highest-risk populations for depression, anxiety, and alcohol use problems, yet no intervention has been tested for efficacy for this population's co-occurring health risks. This first randomized trial of such a treatment shows that a transdiagnostic minority-stress-focused approach has potential to exert robust impact on sexual minority women's mental health. Future research into additional treatment targets, perhaps beyond minority stress, and factors relevant for reducing alcohol use problems, is needed.