Objective: To investigate the value of delta-radiomics after the first cycle of neoadjuvant chemotherapy (NAC) using dynamic contrast-enhanced (DCE) MRI for early prediction of pathological complete response (pCR) in patients with breast cancer. Methods: From September 2018 to May 2021, a total of 140 consecutive patients (training, n = 98: validation, n = 42), newly diagnosed with breast cancer who received NAC before surgery, were prospectively enrolled. All patients underwent DCE-MRI at pre-NAC (pre-) and after the first cycle (1st-) of NAC. Radiomic features were extracted from the postcontrast early, peak, and delay phases. Delta-radiomics features were computed in each contrast phases. Least absolute shrinkage and selection operator (LASSO) and a logistic regression model were used to select features and build models. The model performance was assessed by receiver operating characteristic (ROC) analysis and compared by DeLong test. Results: The delta-radiomics model based on the early phases of DCE-MRI showed a highest AUC (0.917/0.842 for training/validation cohort) compared with that using the peak and delay phases images. The delta-radiomics model outperformed the pre-radiomics model (AUC = 0.759/0.617, p = 0.011/0.047 for training/validation cohort) in early phase. Based on the optimal model, longitudinal fusion radiomic models achieved an AUC of 0.871/0.869 in training/validation cohort. Clinical-radiomics model generated good calibration and discrimination capacity with AUC 0.934 (95%CI: 0.882, 0.986)/0.864 (95%CI: 0.746, 0.982) for training and validation cohort. Delta-radiomics based on early contrast phases of DCE-MRI combined clinicopathology information could predict pCR after one cycle of NAC in patients with breast cancer.