Iliotibial band syndrome (ITBS) is a common running related injury. While previous studies have evaluated the relationship between biomechanical variables and ITBS, most have found limited evidence, particularly with measures related to ground reaction force (GRF). The purpose of this study was to use a classification and regression tree (CART) analysis to determine whether the combination of GRF measures would be strongly associated in runners with ITBS. A cross-sectional study was performed at an outpatient center focused on running injuries. A convenience sample of 52 runners with ITBS, assessed between September 2012 and July 2022, were evaluated for eligibility, from which, 30 rearfoot strike runners with ITBS and no secondary running-related injuries were selected. Injured runners were matched to 30 healthy controls from a normative database. Each ran on an instrumented treadmill at a self-selected speed. GRF variables were calculated, including peak GRFs, loading rates, and impulses. CART analysis was performed to identify interactions between GRF data and runners with ITBS. An ROC curve was executed, to determine the accuracy of the model. Posterior GRF impulse (PGRFI), anterior GRF (AGRFI), peak anterior GRF (PAGRF), and vertical stiffness at initial loading (VSIL) all emerged as variables associated with ITBS in the CART analysis. The model was able to correctly identify 25 (83.3%) runners with ITBS and 25 (83.3%) controls. The area under the ROC curve (accuracy) was 0.87 (95% CI, 0.77–0.96; SE, 0.04; p < 0.001). In conclusion, interactions between GRF variables were associated with ITBS in runners. The best classification included interactions between PGRFI, AGRFI, AGRFP, and VSIL, using specific cut-off values. Loading rates were not independently associated with ITBS.