Background: Pressure injuries (PIs) are increasing worldwide, and there has been no significant improvement in preventing them. Traditional assessment tools are widely used to identify a patient at risk of developing a PI. This study aims to construct a novel fused multi-channel prediction model of PIs in adult hospitalized patients using machine learning algorithms (MLAs). Methods: A multi-phase quantitative approach involving a case–control experimental design was used. A first-hand dataset was collected retrospectively between March/2022 and August/2023 from the electronic medical records of three hospitals in Palestine. Results: The total number of patients was 49,500. A balanced dataset was utilized with a total number of 1110 patients (80% training and 20% testing). The models that were developed utilized eight MLAs, including linear regression and support vector regression (SVR), logistic regression (LR), random forest (RF), gradient boosting (GB), K-nearest neighbor (KNN), decision tree (DT), and extreme gradient boosting (XG boosting) and validated with five-fold cross-validation techniques. The best model was RF, for which the accuracy was 0.962, precision was 0.942, recall was 0.922, F1 was 0.931, area under curve (AUC) was 0.922, false positive rate (FPR) was 0.155, and true positive rate (TPR) was 0.782. Conclusions: The predictive factors were age, moisture, activity, length of stay (LOS), systolic blood pressure (BP), and albumin. A novel fused multi-channel prediction model of pressure injury was developed from different datasets