Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) is caused by motor disinhibition during REM sleep and is a strong early predictor of Parkinson’s disease. However, screening questionnaires for iRBD lack specificity due to other sleep disorders that mimic the symptoms. Nocturnal wrist actigraphy has shown promise in detecting iRBD by measuring sleep-related motor activity, but it relies on sleep diary-defined sleep periods, which are not always available. Our aim was to precisely detect iRBD using actigraphy alone by combining two actigraphy-based markers of iRBD - abnormal nighttime activity and 24-hour rhythm disruption. In a sample of 42 iRBD patients and 42 controls (21 clinical controls with other sleep disorders and 21 community controls) from the Stanford Sleep Clinic, the nighttime actigraphy model was optimized using automated detection of sleep periods. Using a subset of 38 iRBD patients with daytime data and 110 age-, sex-, and body-mass-index-matched controls from the UK Biobank, the 24-hour rhythm actigraphy model was optimized. Both nighttime and 24-hour rhythm features were found to distinguish iRBD from controls. To improve the accuracy of iRBD detection, we fused the nighttime and 24-hour rhythm disruption classifiers using logistic regression, which achieved a sensitivity of 78.9%, a specificity of 96.4%, and an AUC of 0.954. This study preliminarily validates a fully automated method for detecting iRBD using actigraphy in a general population.Clinical relevance— Actigraphy-based iRBD detection has potential for large-scale screening of iRBD in the general population.