Closed femoral shaft fracture is caused by high-energy injuries, and non-union exists after operation, which can significantly damage patients’ body and mind. This study aimed to explore the factors influencing postoperative non-union of closed femoral shaft fractures and establish a predictive nomogram. Patients with closed femoral shaft fractures treated at Hebei Medical University Third Hospital between January 2015 and December 2021 were retrospectively enrolled. A total of 729 patients met the inclusion criteria; of them, those treated in 2015–2019 comprised the training cohort (n = 617), while those treated in 2020–2021 comprised the external validation cohort (n = 112). According to multivariate logistic regression analysis, complex fractures, bone defects, smoking, and postoperative infection were independent risk factors. Based on the factors, a predictive nomogram was constructed and validated. The C-indices in training and external validation cohorts were 0.818 and 0.781, respectively; and the C-index of internal validation via bootstrap resampling was 0.804. The Hosmer–Lemeshow test showed good fit of the nomogram (P > 0.05) consistent with the calibration plot results. The clinical effectiveness was best at a threshold probability of 0.10–0.40 in decision curve analysis. The risk prediction for patients with fractures using this nomogram may aid targeted prevention and rehabilitation programs.