Machine learning algorithms are an important measure with which to perform landslide susceptibility assessments, but most studies use GIS-based classification methods to conduct susceptibility zonation. This study presents a machine learning approach based on the C5.0 decision tree (DT) model and the K-means cluster algorithm to produce a regional landslide susceptibility map. Yanchang County, a typical landslide-prone area located in northwestern China, was taken as the area of interest to introduce the proposed application procedure. A landslide inventory containing 82 landslides was prepared and subsequently randomly partitioned into two subsets: training data (70% landslide pixels) and validation data (30% landslide pixels). Fourteen landslide influencing factors were considered in the input dataset and were used to calculate the landslide occurrence probability based on the C5.0 decision tree model. Susceptibility zonation was implemented according to the cut-off values calculated by the K-means cluster algorithm. The validation results of the model performance analysis showed that the AUC (area under the receiver operating characteristic (ROC) curve) of the proposed model was the highest, reaching 0.88, compared with traditional models (support vector machine (SVM) = 0.85, Bayesian network (BN) = 0.81, frequency ratio (FR) = 0.75, weight of evidence (WOE) = 0.76). The landslide frequency ratio and frequency density of the high susceptibility zones were 6.76/km² and 0.88/km², respectively, which were much higher than those of the low susceptibility zones. The top 20% interval of landslide occurrence probability contained 89% of the historical landslides but only accounted for 10.3% of the total area. Our results indicate that the distribution of high susceptibility zones was more focused without containing more “stable” pixels. Therefore, the obtained susceptibility map is suitable for application to landslide risk management practices.