Federal research grants provide support for the indirect costs (IDCs) of research infrastructure that are not specific to particular research projects but are nonetheless essential to enable research. Institutions independently negotiate IDC rates. The authors sought to identify whether inequities exist in negotiated IDC rates between historically Black colleges and universities (HBCUs) and other universities (non-HBCUs). In 2023, the authors analyzed mean negotiated IDC rates between the top 20 HBCUs (in fiscal year [FY] 2021 research expenditures) and 3 non-HBCU comparison groups: the top 40 non-HBCUs in FY 2021 research expenditures, metropolitan statistical area (MSA)-matched non-HBCUs (among the top 200 institutions by FY 2021 research expenditures), and FY 2021 research expenditure-matched non-HBCUs. The authors found that the top 20 HBCUs' mean IDC rates (50.0%) were, after adjustment, 8.5 percentage points (95% confidence interval [CI], 5.7-11.2) lower than those of the top 40 non-HBCUs (58.5%). The mean IDC rates of top HBCUs (n = 14, 48.4%) were, after adjustment, 6.3 percentage points (95% CI, 3.1-9.4) lower than those of MSA-matched non-HBCUs (n = 23, 55.3%). There was no statistically significant difference in the mean IDC rates between the top 20 HBCUs (50.0%) and expenditure-matched non-HBCUs (n = 31; 48.2%). Inequities in negotiated IDC rates between top HBCUs and non-HBCUs likely both reflect and may contribute to the persistence of institution-level inequities in federally funded research. Proactive investments in HBCUs' research infrastructures are likely needed to ameliorate these funding inequities and support the role of HBCUs in providing opportunity for underrepresented groups in biomedical sciences.