After neoadjuvant chemotherapy (NACT), tumor shrinkage pattern is a more reasonable outcome to decide a possible breast-conserving surgery (BCS) than pathological complete response (pCR). The aim of this article was to establish a machine learning model combining radiomics features from multiparametric MRI (mpMRI) and clinicopathologic characteristics, for early prediction of tumor shrinkage pattern prior to NACT in breast cancer. This study included 199 patients with breast cancer who successfully completed NACT and underwent following breast surgery. For each patient, 4,198 radiomics features were extracted from the segmented 3D regions of interest (ROI) in mpMRI sequences such as T1-weighted dynamic contrast-enhanced imaging (T1-DCE), fat-suppressed T2-weighted imaging (T2WI), and apparent diffusion coefficient (ADC) map. The feature selection and supervised machine learning algorithms were used to identify the predictors correlated with tumor shrinkage pattern as follows: (1) reducing the feature dimension by using ANOVA and the least absolute shrinkage and selection operator (LASSO) with 10-fold cross-validation, (2) splitting the dataset into a training dataset and testing dataset, and constructing prediction models using 12 classification algorithms, and (3) assessing the model performance through an area under the curve (AUC), accuracy, sensitivity, and specificity. We also compared the most discriminative model in different molecular subtypes of breast cancer. The Multilayer Perception (MLP) neural network achieved higher AUC and accuracy than other classifiers. The radiomics model achieved a mean AUC of 0.975 (accuracy = 0.912) on the training dataset and 0.900 (accuracy = 0.828) on the testing dataset with 30-round 6-fold cross-validation. When incorporating clinicopathologic characteristics, the mean AUC was 0.985 (accuracy = 0.930) on the training dataset and 0.939 (accuracy = 0.870) on the testing dataset. The model further achieved good AUC on the testing dataset with 30-round 5-fold cross-validation in three molecular subtypes of breast cancer as following: (1) HR+/HER2-: 0.901 (accuracy = 0.816), (2) HER2+: 0.940 (accuracy = 0.865), and (3) TN: 0.837 (accuracy = 0.811). It is feasible that our machine learning model combining radiomics features and clinical characteristics could provide a potential tool to predict tumor shrinkage patterns prior to NACT. Our prediction model will be valuable in guiding NACT and surgical treatment in breast cancer.