Abstract Objective To evaluate the efficacy of the CT-based intratumoral, peritumoral, and combined radiomics signatures in predicting progression-free survival (PFS) of patients with chondrosarcoma (CS). Methods In this study, patients diagnosed with CS between January 2009 and January 2022 were retrospectively screened, and 214 patients with CS from two centers were respectively enrolled into the training cohorts (institution 1, n = 113) and test cohorts (institution 2, n = 101). The intratumoral and peritumoral radiomics features were extracted from CT images. The intratumoral, peritumoral, and combined radiomics signatures were constructed respectively, and their radiomics scores (Rad-score) were calculated. The performance of intratumoral, peritumoral, and combined radiomics signatures in PFS prediction in patients with CS was evaluated by C-index, time-dependent area under the receiver operating characteristics curve (time-AUC), and time-dependent C-index (time C-index). Results Eleven, 7, and 16 features were used to construct the intratumoral, peritumoral, and combined radiomics signatures, respectively. The combined radiomics signature showed the best prediction ability in the training cohort (C-index, 0.835; 95%; confidence interval [CI], 0.764–0.905) and the test cohort (C-index, 0.800; 95% CI, 0.681–0.920). Time-AUC and time C-index showed that the combined signature outperformed the intratumoral and peritumoral radiomics signatures in the prediction of PFS. Conclusion The CT-based combined signature incorporating intratumoral and peritumoral radiomics features can predict PFS in patients with CS, which might assist clinicians in selecting individualized surveillance and treatment plans for CS patients. Critical relevance statement Develop and validate CT-based intratumoral, peritumoral, and combined radiomics signatures to evaluate the efficacy in predicting prognosis of patients with CS. Key points • Reliable prognostic models for preoperative chondrosarcoma are lacking. • Combined radiomics signature incorporating intratumoral and peritumoral features can predict progression-free survival in patients with chondrosarcoma. • Combined radiomics signature may facilitate individualized stratification and management of patients with chondrosarcoma. Graphical Abstract