<p>An extensive research literature describes how close social connections (CSC) comprising both intimate friends and relatives and friends who help when in trouble are one of the most significant predictors of improved well-being outcomes, approximately equivalent to a 5-fold increase in income, in some contexts. However, less is known about childhood predictors of adulthood CSC, including what childhood factors have potency across diverse cultural settings. We use data from a diverse sample of 202,898 individuals across 22 countries to evaluate the influence of several childhood factors on CSC in adulthood (mean age = 42.3 years, SD 15.9, range 18–99). Childhood predictors associated with increased CSC include physical health, family financial status, maternal and paternal relationships, and religious service attendance. Childhood predictors associated with decreased CSC include poor heath, being an outsider in the family, unmarried parents, and very difficult financial status of the family. The strength of these associations varies by country, reflecting diverse societal influences, ranging, for example, from a strong positive association to as strong a negative association or twice as strong a positive association (e.g., Relationship to Mother ranged from meta-analytic mean of β = 0.47 to β=-0.35 in one country and β = 0.93 in another). We use multivariate regression analysis and E-values to check the robustness of the findings against potential unmeasured confounds. The findings enhance our understanding of childhood predictors of adult levels of CSC, providing valuable evidence for practical interventions and policy for developing early childhood intervention approaches to promoting the CSC that impact whole-human well-being. These interventions should consider multiple childhood factors relevant to enhancing close social connections in adulthood and should be attuned to the cultural context and patterns of inequality within countries.</p>