During the COVID-19 pandemic, families have experienced unprecedented financial and social disruptions. We studied the impact of preexisting psychosocial factors and pandemic-related financial and social disruptions in relation to family well-being among N = 4091 adolescents and parents during early summer 2020, participating in the Adolescent Brain Cognitive DevelopmentSM Study. Poorer family well-being was linked to prepandemic psychosocial and financial adversity and was associated with pandemic-related material hardship and social disruptions to routines. Parental alcohol use increased risk for worsening of family relationships, while a greater endorsement of coping strategies was mainly associated with overall better family well-being. Financial and mental health support may be critical for family well-being during and after a widespread crisis, such as the COVID-19 pandemic.