The object of this study was to demonstrate the ability of machine learning (ML) methods for the segmentation and classification of diabetic retinopathy (DR). Two-dimensional (2D) retinal fundus (RF) images were used. The datasets of DR-that is, the mild, moderate, non-proliferative, proliferative, and normal human eye ones-were acquired from 500 patients at Bahawal Victoria Hospital (BVH), Bahawalpur, Pakistan. Five hundred RF datasets (sized 256 × 256) for each DR stage and a total of 2500 (500 × 5) datasets of the five DR stages were acquired. This research introduces the novel clustering-based automated region growing framework. For texture analysis, four types of features-histogram (H), wavelet (W), co-occurrence matrix (COM) and run-length matrix (RLM)-were extracted, and various ML classifiers were employed, achieving 77.67%, 80%, 89.87%, and 96.33% classification accuracies, respectively. To improve classification accuracy, a fused hybrid-feature dataset was generated by applying the data fusion approach. From each image, 245 pieces of hybrid feature data (H, W, COM, and RLM) were observed, while 13 optimized features were selected after applying four different feature selection techniques, namely Fisher, correlation-based feature selection, mutual information, and probability of error plus average correlation. Five ML classifiers named sequential minimal optimization (SMO), logistic (Lg), multi-layer perceptron (MLP), logistic model tree (LMT), and simple logistic (SLg) were deployed on selected optimized features (using 10-fold cross-validation), and they showed considerably high classification accuracies of 98.53%, 99%, 99.66%, 99.73%, and 99.73%, respectively.