Family is an important socialization context for youth as they move through early adolescence. A significant feature of this complex socialization context is the accumulation of potential family risk factors that may compromise youth adjustment. This study examined cumulative family risk and adolescents’ adjustment difficulties in 416 two-parent families using four waves of annual longitudinal data (51 % female youth). Risk factors in four family domains were examined: socioeconomic, parents’ psychological realm, marital, and parenting. Cumulative family risk experienced while in 6th grade was associated concurrently with daughters’ higher internalizing problems and with increased internalizing problems during early adolescence. Cumulative family risk was associated concurrently with sons’ higher externalizing problems and with daughters’ increased externalizing problems over time. Cumulative family risk was associated concurrently with lower grades and with declining grades over time for both daughters and sons. The number of risk domains also was associated with youths’ adjustment difficulties during early adolescence, providing evidence that risk in two-parent families involves more than ineffective parenting. These findings suggest a critical need to provide strong support for families in reducing a variety of stressors across multiple family domains as their children traverse early adolescence.