Socioeconomic disadvantage is associated with larger COVID-19 disease burdens and pandemic-related economic impacts. We utilized the longitudinal Adolescent Brain Cognitive Development Study to understand how family- and neighborhood-level socioeconomic disadvantage relate to disease burden, family communication, and preventative responses to the pandemic in over 6,000 youth-parent/caregiver dyads. Data were collected at three timepoints (May to August 2020). Here, we show that both family- and neighborhood-level disadvantage were associated with parents’ reports of greater family COVID-19 exposure risk and diagnoses, less perceived exposure risk, more frequent parent-youth conversations about COVID-19 risk/prevention and reassurance, and greater youth preventative behaviors. More disadvantaged families may be adaptively incorporating more protective strategies to reduce emotional distress and likelihood of COVID-19 infection. The results highlight the importance of parent-youth communication and disease-preventative practices for buffering the economic and disease burdens of COVID-19, along with policies and programs that reduce these burdens for families with socioeconomic disadvantage.