To compare the capabilities of three-dimensional contrast enhanced ultrasound (3D-CEUS) and dynamic contrast-enhanced magnetic resonance (DCE-MRI) in predicting the response to neoadjuvant chemotherapy (NAC) among breast cancer patients, 48 patients with unilateral breast cancer were recruited for 3D-CEUS and DCE-MRI examinations both before and after NAC; pathology was used to validate the results. This study was approved by the institutional review board, and written informed consent was obtained from each patient. Imaging feature changes and pathological vascularity response, including microvessel density (MVD) and vascular endothelial growth factor (VEGF), were calculated. Pathological complete response (pCR) and major histological response (MHR) were used as references. The 3D-CEUS score, DCE-MRI score, MVD and VEGF significantly decreased (P < 0.0001) after NAC. The correlations between Δ3D-CEUS and ΔDCE-MRI with pCR (r = 0.649, P < 0.0001; r = 0.639, P < 0.0001) and MHR (r = 0.863, P < 0.0001; r = 0.836, P < 0.0001) were significant. All scores showed significant differences between the pCR and non-pCR groups with folder changes of 0.1, 0.1, 2.4, and 2.3, respectively (P = 0.0001, <0.0001, <0.0001 and <0.0001). In conclusion, 3D-CEUS is effective in assessing the response of breast cancer patients undergoing NAC.