Background: Given improvements in systemic therapy, pathologic complete response (pCR) rates following neoadjuvant chemotherapy were over 60% in breast cancer patients in recent clinical trials, especially in human epidermal growth factor receptor 2 (HER2)-positive and triple negative cases. While racial minority groups were associated with worse survival outcomes despite receiving standard of care in prospective studies, they were under-represented in clinical trials. To address this knowledge gap, we performed an observational cohort study to evaluate pCR and survival outcomes stratified by racial and ethnic groups. Methods: The National Cancer Database (NCDB) was queried for female patients with stage I-III breast cancer diagnosed between 2010 and 2017 treated with neoadjuvant chemotherapy followed by surgery. Cochran-Armitage test was used to analyze the trend of pCR over time. Logistic multivariable analysis (MVA) was used to identify variables associated with pCR defined as ypT0/isN0. Cox MVA was used to analyze the overall survival (OS) benefit. Results: A total of 105,804 patients (n = 72,631 for non-Hispanic white [NHW], n = 7,632 for Hispanic white [HW], n = 19,505 for black, n = 4,393 for Asian or Pacific Islander [API], n = 1,643 for other race) were included for analysis. Median follow up was 49.2 months (interquartile range 32.7-71.3). Overall pCR rate increased from 15.1% in 2010 to 27.2% in 2017, largely driven by API women (15.7% to 31.6%) and hormone receptor (HR)-HER2+ tumors (28.6% to 53.1%; all trend p < 0.001). On logistic MVA, when compared to NHW women, HW women were more likely to have pCR for HR-HER2+ (adjusted odds ratio [aOR] 1.18, p = 0.02) and HR+HER2+ tumors (aOR 1.29, p = 0.005), while black women were more likely to have pCR for HR+HER2- tumors (aOR 1.13, p = 0.01) and less likely for HR-HER2+ (aOR 0.80, p < 0.001) and triple negative tumors (aOR 0.82, p < 0.001). API women were more likely to have pCR for HR-HER2+ tumors compared to NHW women (aOR 1.17, p = 0.04). On Cox MVA, when compared to NHW women, HW (ypT+N0: adjusted hazards ratio [aHR] 0.75, p < 0.001; ypN+: aHR 0.79, p < 0.001) and API women (ypT0/isN0: aHR 0.52, p = 0.005; ypT+N0: aHR 0.63, p < 0.001; ypN+: aHR 0.86, p = 0.03) were associated with improved OS, while black women were associated with worse OS for ypN+ only (aHR 1.18, p < 0.001). Conclusions: To our knowledge, this is the largest study using a nationwide oncology database suggesting the improving trend of pCR rate over time for all racial cohorts. In our study, when compared to NHW, HW and API women were more likely to have pCR for select HER2+ tumors, while black women were less likely to have pCR for HR-HER2+ and triple negative tumors but not for HR+HER2- tumors. HW and API women were associated with improved survival in the setting of any residual disease compared to NHW women, while black women were associated with worse survival only for residual nodal disease.