Running biomechanics are affected by fatiguing or prolonged runs. However, no evidence to date has conclusively linked this effect to running-related injury (RRI) development or performance implications. Previous investigations using subject-specific models in running have demonstrated higher accuracy than group-based models, however, this has been infrequently applied to fatigue. In this study, two experiments were conducted to determine whether subject-specific models outperformed group-based models to classify running biomechanics during non-fatigued and fatigued conditions. In the first experiment, 16 participants performed four treadmill runs at or around the maximal lactate steady state. In the second experiment, nine participants performed five prolonged runs using commercial wearable devices. For each experiment, two segments were extracted from each trial from early and late in the run. For each participant, a random forest model was applied with a leave-one-run-out cross-validation to classify between the early (non-fatigued) and late (fatigued) segments. Additionally, group-based classifiers with a leave-one-subject-out cross validation were constructed. For experiment 1, mean classification accuracies for the single-subject and group-based classifiers were 68.2 ± 8.2% and 57.0 ± 8.9%, respectively. For experiment 2, mean classification accuracies for the single-subject and group-based classifiers were 68.9 ± 17.1% and 61.5 ± 11.7%, respectively. Variable importance rankings were consistent within participants, but these rankings differed from each participant to those of the group. Although the classification accuracies were relatively low, these findings highlight the advantage of subject-specific classifiers to detect changes in running biomechanics with fatigue and indicate the potential of using big data and wearable technology approaches in future research to determine possible connections between biomechanics and RRI.