Background: Chest X-ray has been included in national tuberculosis screening algorithms as a sensitive tuberculosis screening tool among high-risk groups. However, the implementation was influenced by multiple factors. We aimed to explore facilitators and barriers to implementing chest X-ray in systematic tuberculosis screening of clinically high-risk groups in Addis Ababa, Ethiopia. Methods: We conducted face-to-face, in-depth interviews with purposively selected participants at tertiary-level hospitals and a tuberculosis program coordinator at the Ethiopian Ministry of Health, who coordinates chest X-ray-guided systematic tuberculosis screening. A framework analysis was conducted using the consolidated framework for implementation research. Results: We identified 11 constructs that influenced the implementation of the chest X-ray intervention. Facilitators included the relative sensitivity of chest X-ray over symptom-based screening, its potential integration into existing systems, technological advancements in the area, policies and laws supporting the screening intervention, and the quality of the evidence of the screening intervention. Barriers included implementation complexity, high costs of the intervention, knowledge gaps among healthcare providers, training gaps, low priority for chest X-ray screening at the healthcare facility level, and a lack of external support from the Ministry of Health and stakeholders. Conclusion: This study identified contextual factors that influence the implementation of chest X-ray guided systematic tuberculosis screening among clinically high-risk groups that healthcare facilities and health ministries may use for decision-making. Addressing the barriers identified by the study would help to improve the implementation of chest X-rays for improved tuberculosis case detection and prompt treatment in clinically high-risk groups.