Links between positive and negative aspects of the parent-child relationship and child adjustment are undisputed. Scholars recognize the importance of parental differential treatment (PDT) of siblings, yet, less is known about PDT in the context of the shared (family-wide) parent-child relationship climate, or about the extent to which positivity may buffer children’s adjustment from negativity. Controlling for behavioral stability, we examined the potential for positive and negative parent-child processes to interact across and between child-specific and family-wide levels in the prediction of children’s adjustment. Specifically, in a sample of 2,039 United Kingdom families, we used multilevel models to examine child-specific and family-wide mother-child relationships (at 4 years)—including interactive processes—in the prediction of prosocial behavior and conduct problems (at 7 years). The majority of variance in children’s adjustment resided within-families: siblings were strikingly different. Accounting for behavioral stability, family-wide negativity and negative PDT associated with both prosociality and conduct problems. More important, we demonstrated interactions between, (a) family-wide negativity and negative PDT for conduct problems, as well as, (b) positive and negative PDT in the prediction of both prosocial behavior and conduct problems. Results suggest negative PDT associates with increased conduct problems over time, even when the overall family climate is low in negativity. They also indicate a buffering role of positive PDT on the deleterious effects of negative PDT for children’s adjustment. Implications for both research and practice are discussed, including the importance of information gained by considering more than one child in the family.