© 2016 American Society for Nutrition. Background: Bodymass index (BMI, in kg/m2) is positively associatedwith plasma glucose in late pregnancy andwith risk of adverse obstetric outcomes. Much of the existing research uses single-clinic measures of plasma glucose, which may not accurately reflect circulating glucose under free-living conditions. Furthermore, little is known about circulating glucose concentrations of African Americanwomen, who tend to have poorer diet quality and a greater risk of obstetric complications. Objective: The objective of the study was to test the hypothesis that the positive association of BMI in early pregnancy with third-trimester circulating glucose concentrations measured under free-living conditions among African American womenwould be at least partially attributable to lower β-cell insulin secretion relative to insulin sensitivity [i.e., lower disposition index (DI)]. Methods: Using a prospective, observational design, 40 pregnant African American women (mean ± SD age: 23.1 ± 4.0 y; mean ± SD BMI: 28.4 ± 7.5) wore continuous glucose monitors and accelerometers for 3 d at 32-35 wk of gestation and concurrently maintained a food diary to report their self-selected meals. The DI was derived from a 75-g oral glucose tolerance test. Linear regression modeling was used to calculate the association of BMI with the 24-h glucose (GLUC24h) and 2-h (GLUC2hPP) postprandial glucose areas under the curve and with the percentage of time the glucose concentrations were > 120 mg/dL. Results: The positive associations between BMI and GLUC24h (standardized b = 0.36, P = 0.03) and the percentage of time glucose concentrations were > 120 mg/dL (standardized b = 0.40, P = 0.02) were independent of total carbohydrate intake and physical activity and were attenuated when DI was added to the model. The positive association of BMI with GLUC2hPP was attenuated when DI was added to the model, and DI itself was independently associated with GLUC2hPP after self-selected breakfast and dinner (standardized b = 20.33 and 20.42, respectively; P = 0.01). Conclusions: The association of BMI with high circulating glucose in free-living pregnant African American women is at least partially attributable to lower β-cell responsiveness.