**Abstract** **Objective:** Gender minority youth (i.e., children/adolescents whose gender identity and/or expression is inconsistent with their birth-assigned sex) experience elevated rates of emotional and behavioral problems relative to cisgender youth (who identify with their birth-assigned sex), which are not intrinsic to gender identity but attributable to unique minority stressors. Although empirically-supported treatments have proven effective in treating these mental health concerns generally, randomized controlled trials have not examined effects for gender minority youth. **Method:** To address this gap, we pooled data from clinically-referred youth (N = 432; M(SD)age = 10.6(2.2); 55.1% White) assigned to empirically-supported treatment conditions across four previous randomized controlled trials of modular psychotherapy. A proxy indicator of gender identity (i.e., youth’s wish to be the opposite sex) was used to classify gender minority (n = 64) and cisgender (n = 368) youth. Youth- and caregiver-reported pretreatment internalizing and externalizing problems, treatment effectiveness on these domains, and treatment acceptability were compared across groups. **Results:** Gender minority youth reported more severe pretreatment internalizing and externalizing problems compared to cisgender youth; in contrast, their caregivers reported less severe problems. Though treatment was equally effective for both groups on most outcomes, gender minority youth’s caregiver-reported externalizing problems improved more slowly and less reliably, and their self-reported internalizing problems were more likely to remain clinically elevated. Further, gender minority youth reported lower treatment satisfaction. **Conclusions:** While findings suggest that empirically-supported treatments may effectively address many mental health problems for gender minority youth, they also underscore the need for treatment enhancements that improve acceptability and outcomes. **Public Significance:** This study examined the effectiveness and acceptability of empirically-supported mental health treatments for gender minority youth (who endorsed a wish to be the opposite sex) and cisgender youth. Gender minority youth reported more severe problems before treatment, demonstrated slower improvement in caregiver-reported behavior problems, and endorsed lower treatment satisfaction. Findings support the potential need for provider-focused trainings relevant to gender minority youth.