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Background The education sector is one of the most common and accessible settings for universal prevention programs for youth mental health. But it suffers from suboptimal implementation of evidence-based practices (EBPs). Although the organizational context (OC) contains crucial implementation factors, successful implementation ultimately resides in the behavioral and cognitive factors of individual implementers (e.g., attitudes toward EBPs). Also, emerging literature called for discerning the general and strategic types of OC factors and exploring their interaction effect on individual implementation behaviors. This study aimed to examine the cross-level associations among implementer attitudes toward EBPs and leadership and climate (general and strategic) at the individual and organizational-levels and their mechanistic interaction effect. Methods A series of multilevel models (MLMs) were fitted on a diverse sample of educational agencies actively implementing universal prevention programs for youth mental health (441 implementers from 52 schools). The organization-level aggregates and individual perceptions of general and strategic leadership and climate, and their interaction terms, were entered as level-2 and level-1 predictors based on their level of measurement. The outcomes are four dimensions of implementer attitudes toward EBPs (Requirement, Openness, Appeal, and Divergence). Results At the organizational level, higher levels of strategic leadership and climate, but not their general counterparts, were consistently associated with more favorable attitudes in all four dimensions. At the individual level, higher levels of perceived general and strategic leadership and climate were associated with more favorable attitudes of Requirement and Openness. But only general leadership and climate showed significant associations with Appeal. At the organizational-level, general climate moderated the positive effect of strategic climate on implementers' perception of appeal and divergence of EBPs. Conclusions Leaders supporting EBP implementation need to selectively allocate resources on strategic and/or general OC factors, because (a) the associations between implementer attitudes toward EBPs and climate and leadership varied across the level of measurement, specificity to implementation, and attitudinal dimensions; and (b) general climate moderates the effect of strategic climate on whether implementers perceive EBPs as appealing or useless. Limitations and implications for research and practice are discussed and extended to general youth mental health settings.