Abstract Background Examining the role of modifiable barriers and facilitators is a necessary step toward developing effective implementation strategies. This study examines whether both general (organizational culture, organizational climate, and transformational leadership) and strategic (implementation climate and implementation leadership) organizational-level factors predict therapist-level determinants of implementation (knowledge of and attitudes toward evidence-based practices). Methods Within the context of a system-wide effort to increase the use of evidence-based practices (EBPs) and recovery-oriented care, we conducted an observational, cross-sectional study of 19 child-serving agencies in the City of Philadelphia, including 23 sites, 130 therapists, 36 supervisors, and 22 executive administrators. Organizational variables included characteristics such as EBP initiative participation, program size, and proportion of independent contractor therapists; general factors such as organizational culture and climate (Organizational Social Context Measurement System) and transformational leadership (Multifactor Leadership Questionnaire); and strategic factors such as implementation climate (Implementation Climate Scale) and implementation leadership (Implementation Leadership Scale). Therapist-level variables included demographics, attitudes toward EBPs (Evidence-Based Practice Attitudes Scale), and knowledge of EBPs (Knowledge of Evidence-Based Services Questionnaire). We used linear mixed-effects regression models to estimate the associations between the predictor (organizational characteristics, general and strategic factors) and dependent (knowledge of and attitudes toward EBPs) variables. Results Several variables were associated with therapists’ knowledge of EBPs. Clinicians in organizations with more proficient cultures or higher levels of transformational leadership (idealized influence) had greater knowledge of EBPs; conversely, clinicians in organizations with more resistant cultures, more functional organizational climates, and implementation climates characterized by higher levels of financial reward for EBPs had less knowledge of EBPs. A number of organizational factors were associated with the therapists’ attitudes toward EBPs. For example, more engaged organizational cultures, implementation climates characterized by higher levels of educational support, and more proactive implementation leadership were all associated with more positive attitudes toward EBPs. Conclusions This study provides evidence for the importance of both general and strategic organizational determinants as predictors of knowledge of and attitudes toward EBPs. The findings highlight the need for longitudinal and mixed-methods studies that examine the influence of organizational factors on implementation.