Family members’ reactions to youth identity disclosure are important predictors of well-being for lesbian, gay, bisexual, transgender, queer, or questioning (LGBTQ) youth. To better understand potential variation within and across families’ current reactions, this study established latent profiles of family level reaction patterns and examined predictors and outcomes associated with these patterns. In 2011–2012, LGBTQ youth (N = 447, Mage = 18.8) rated their mother’s, father’s, brother’s, and sister’s reactions to their LGBTQ identity and reported their own depressive symptoms and self-esteem. Latent profile analysis tested patterns of family members’ reactions. Most participants reported either moderately positive reactions (49.2%) or very positive reactions (34.0%) from all family members, though 16.8% of youth reported negative reactions from all family members. Youth social positions and demographic factors predicted profile membership: transgender youth, youth-assigned male at birth, older age at first disclosure predicted membership in the negative family reaction profile, whereas gay youth, having a parent and/or sibling with an LGBTQ identity, coresidence with either mothers, fathers, or siblings, and more years since first disclosure predicted membership in the very positive family reaction profile. Multiracial youth and younger youth were more likely to be in the moderately positive family reaction profile. Youth in families characterized by negative reactions had higher depressive symptoms and lower self-esteem compared to those who reported moderately positive or very positive reactions. Findings underscore the interconnectedness of family members’ reactions and suggest that interventions for LGBTQ youth with rejecting and/or less accepting family members may need to target the entire family system.