Life events and reward-system functioning contribute to resilience and risk for depression. However, interactions between life events and neural responses to reward and loss have not been previously investigated in relation to depression symptoms in child and adolescent populations. An unselected sample (N = 130) of 8- to 14-year-old girls (mean = 12.6 years) completed the Child Depression Inventory and a functional magnetic resonance imaging guessing task in which they won or lost money on each trial. Parents completed a measure of life events experienced by the child. Life events were separated by positive versus negative and whether they were likely related or unrelated to the daughter's behavior (i.e., dependent vs. independent, respectively). Multiple regressions tested whether the interaction between ventral striatal (VS) response to wins or losses and recent life events were associated with child-reported depressive symptoms. A greater number of dependent positive life events related to decreased total depression symptoms when VS response to wins was robust. Conversely, a greater number of independent negative life events related to increased negative mood depression symptoms when VS response to losses was robust; this relationship was in the opposite direction when VS response to loss was low. VS response to reward and loss were independent moderators of the relationship between recent life events (positive and negative, respectively) and depressive symptoms. Findings suggest that targeting neural responses (i.e., increasing responses to winning or decreasing responses to losing) may be important for both improving resilience and reducing risk in different environmental contexts.