Purpose: To evaluate the ability of radiomics score (RS)–based machine learning to identify moderate to severe coronary artery calcium (CAC) on chest x-ray radiographs (CXR). Materials and Methods: We included 559 patients who underwent a CAC scan with CXR obtained within 6 months and divided them into training (n = 391) and validation (n = 168) cohorts. We extracted radiomic features from annotated cardiac contours in the CXR images and developed an RS through feature selection with the least absolute shrinkage and selection operator regression in the training cohort. We evaluated the incremental value of the RS in predicting CAC scores when combined with basic clinical factor in the validation cohort. To predict a CAC score ≥100, we built an RS-based machine learning model using random forest; the input variables were age, sex, body mass index, and RS. Results: The RS was the most prominent factor for the CAC score ≥100 predictions (odds ratio = 2.33; 95% confidence interval: 1.62-3.44; P < 0.001) compared with basic clinical factor. The machine learning model was tested in the validation cohort and showed an area under the receiver operating characteristic curve of 0.808 (95% confidence interval: 0.75-0.87) for a CAC score ≥100 predictions. Conclusions: The use of an RS-based machine learning model may have the potential as an imaging marker to screen patients with moderate to severe CAC scores before diagnostic imaging tests, and it may improve the pretest probability of detecting coronary artery disease in clinical practice.