Purpose To predict pathological complete response (pCR) after neoadjuvant chemotherapy using extreme gradient boosting (XGBoost) with MRI and non-imaging data at multiple treatment timepoints. Material and methods This retrospective study included breast cancer patients (n = 117) who underwent neoadjuvant chemotherapy. Data types used included tumor ADC values, diffusion-weighted and dynamic-contrast-enhanced MRI at three treatment timepoints, and patient demographics and tumor data. GLCM textural analysis was performed on MRI data. An extreme gradient boosting machine learning algorithm was used to predict pCR. Prediction performance was evaluated using the area under the curve (AUC) of the receiver operating curve along with precision and recall. Results Prediction using texture features of DWI and DCE images at multiple treatment time points (AUC = 0.871; 95% CI: (0.768, 0.974; p<0.001) and (AUC = 0.903 95% CI: 0.854, 0.952; p<0.001) respectively), outperformed that using mean tumor ADC (AUC = 0.850 (95% CI: 0.764, 0.936; p<0.001)). The AUC using all MRI data was 0.933 (95% CI: 0.836, 1.03; p<0.001). The AUC using non-MRI data was 0.919 (95% CI: 0.848, 0.99; p<0.001). The highest AUC of 0.951 (95% CI: 0.909, 0.993; p<0.001) was achieved with all MRI and all non-MRI data at all time points as inputs. Conclusion Using XGBoost on extracted GLCM features and non-imaging data accurately predicts pCR. This early prediction of response can minimize exposure to toxic chemotherapy, allowing regimen modification mid-treatment and ultimately achieving better outcomes.