Background: Colposcopy plays an essential role in cervical cancer control, but its performance remains unsatisfactory. This study evaluates the feasibility of machine learning (ML) models for predicting high-grade squamous intraepithelial lesions or worse (HSIL+) in patients referred for colposcopy by combining colposcopic findings with demographic and screening results. Methods: In total, 7485 patients who underwent colposcopy examination in seven hospitals in mainland China were used to train, internally validate, and externally validate six commonly used ML models, including logistic regression, decision tree, naïve bayes, support vector machine, random forest, and extreme gradient boosting. Nine variables, including age, gravidity, parity, menopause status, cytological results, high-risk human papillomavirus (HR-HPV) infection type, HR-HPV multi-infection, transformation zone (TZ) type, and colposcopic impression, were used for model construction. Results: Colposcopic impression, HR-HPV results, and cytology results were the top three variables that determined model performance among all included variables. In the internal validation set, six ML models that integrated demographics, screening results, and colposcopic impression showed significant improvements in the area under the curve (AUC) (0.067 to 0.099) and sensitivity (11.55% to 14.88%) compared with colposcopists. Greater increases in AUC (0.087 to 0.119) and sensitivity (17.17% to 22.08%) were observed in the six models with the external validation set. Conclusions: By incorporating demographics, screening results, and colposcopic impressions, ML improved the AUC and sensitivity for detecting HSIL+ in patients referred for colposcopy. Such models could transform the subjective experience into objective judgments to help clinicians make decisions at the time of colposcopy examinations.