Background The development and application of clinical prediction models using machine learning in clinical decision support systems is attracting increasing attention. Objective The aims of this study were to develop a prediction model for cardiac arrest in the emergency department (ED) using machine learning and sequential characteristics and to validate its clinical usefulness. Methods This retrospective study was conducted with ED patients at a tertiary academic hospital who suffered cardiac arrest. To resolve the class imbalance problem, sampling was performed using propensity score matching. The data set was chronologically allocated to a development cohort (years 2013 to 2016) and a validation cohort (year 2017). We trained three machine learning algorithms with repeated 10-fold cross-validation. Results The main performance parameters were the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). The random forest algorithm (AUROC 0.97; AUPRC 0.86) outperformed the recurrent neural network (AUROC 0.95; AUPRC 0.82) and the logistic regression algorithm (AUROC 0.92; AUPRC=0.72). The performance of the model was maintained over time, with the AUROC remaining at least 80% across the monitored time points during the 24 hours before event occurrence. Conclusions We developed a prediction model of cardiac arrest in the ED using machine learning and sequential characteristics. The model was validated for clinical usefulness by chronological visualization focused on clinical usability.