The treadmill is widely used in running fatigue experiments, and the variation of plantar mechanical parameters caused by fatigue and gender, as well as the prediction of fatigue curves by a machine learning algorithm, play an important role in providing different training programs. This experiment aimed to compare changes in peak pressure (PP), peak force (PF), plantar impulse (PI), and gender differences of novice runners after they were fatigued by running. A support vector machine (SVM) was used to predict the fatigue curve according to the changes in PP, PF, and PI before and after fatigue. 15 healthy males and 15 healthy females completed two runs at a speed of 3.3 m/s ± 5% on a footscan pressure plate before and after fatigue. After fatigue, PP, PF, and PI decreased at hallux (T1) and second-fifth toes (T2–5), while heel medial (HM) and heel lateral (HL) increased. In addition, PP and PI also increased at the first metatarsal (M1). PP, PF, and PI at T1 and T2–5 were significantly higher in females than in males, and metatarsal 3–5 (M3–5) were significantly lower in females than in males. The SVM classification algorithm results showed the accuracy was above average level using the T1 PP/HL PF (train accuracy: 65%; test accuracy: 75%), T1 PF/HL PF (train accuracy: 67.5%; test accuracy: 65%), and HL PF/T1 PI (train accuracy: 67.5%; test accuracy: 70%). These values could provide information about running and gender-related injuries, such as metatarsal stress fractures and hallux valgus. Application of the SVM to the identification of plantar mechanical features before and after fatigue. The features of the plantar zones after fatigue can be identified and the learned algorithm of plantar zone combinations with above-average accuracy (T1 PP/HL PF, T1 PF/HL PF, and HL PF/T1 PI) can be used to predict running fatigue and supervise training. It provided an important idea for the detection of fatigue after running.