Many models using the aid of artificial intelligence have been recently proposed to predict the progression of knee osteoarthritis. However, previous models have not been properly validated with an external data set or have reported poor predictive performances. Therefore, the purpose of this study was to design a machine learning model for knee osteoarthritis progression, focusing on high validation quality and clinical applicability. A retrospective analysis was conducted on prospectively collected data, using the Osteoarthritis Initiative data set (5966 knees) for model development and the Multicenter Osteoarthritis Study data set (3392 knees) for validation. The analysis aimed to predict Kellgren–Lawrence grade (KLG) progression over 4–5 years in knees with initial KLG of 0, 1, or 2. Possible predictors included demographics, comorbidities, history of meniscectomy, gait speed, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and radiological findings. The Random Forest algorithm was employed for the predictive model development. Baseline KLG, contralateral knee osteoarthritis, lateral joint space narrowing (JSN) grade, BMI, medial JSN grade, and total WOMAC score were six features selected for the model in descending order of importance. Odds ratios of baseline KLG, contralateral knee osteoarthritis, and lateral JSN grade were 1.76, 2.59, and 4.74, respectively (all p < 0.001). The area-under-the-curve of the ROC curve in the validation set was 0.76 with an accuracy of 0.68 and an F1-score of 0.56. The progression of knee osteoarthritis in 4 ~ 5 years could be well-predicted using easily available variables. This simple and validated model may aid surgeons in knee osteoarthritis patient management.