Abstract Background Identifying persons with a high risk of developing osteoporosis and preventing the occurrence of the first fracture is a health care priority. Most existing osteoporosis screening tools have high sensitivity but relatively low specificity. Objective We aimed to develop an easily accessible and high-performance preclinical risk screening tool for osteoporosis using a machine learning–based method among the Hong Kong Chinese population. Methods Participants aged 45 years or older were enrolled from 6 clinics in the 3 major districts of Hong Kong. The potential risk factors for osteoporosis were collected through a validated, self-administered questionnaire and then filtered using a machine learning–based method. Bone mineral density was measured with dual-energy x-ray absorptiometry at the clinics; osteoporosis was defined as a t score of −2.5 or lower. We constructed machine learning models, including gradient boosting machines, support vector machines, and naive Bayes, as well as the commonly used logistic regression models, for the prediction of osteoporosis. The best-performing model was chosen as the final tool, named the Preclinical Osteoporosis Screening Tool (POST). Model performance was evaluated by the area under the receiver operating characteristic curve (AUC) and other metrics. Results Among the 800 participants enrolled in this study, the prevalence of osteoporosis was 10.6% (n=85). The machine learning–based Boruta algorithm identified 15 significantly important predictors from the 113 potential risk factors. Seven variables were further selected based on their accessibility and convenience for daily self-assessment and health care practice, including age, gender, education level, decreased body height, BMI, number of teeth lost, and the intake of vitamin D supplements, to construct the POST. The AUC of the POST was 0.86 and the sensitivity, specificity, and accuracy were all 0.83. The positive predictive value, negative predictive value, and F₁-score were 0.41, 0.98, and 0.56, respectively. Conclusions The machine learning–based POST was conveniently accessible and exhibited accurate discriminative capabilities for the prediction of osteoporosis; it might be useful to guide population-based preclinical screening of osteoporosis and clinical decision-making.