(1) Background: Female body composition undergoes significant changes to support fetal growth and development during pregnancy. This study investigated the association of maternal body composition in the second trimester and macrosomia and explored whether body-composition-related indicators could be used to predict macrosomia. (2) Methods: This study was conducted in China from December 2016 to December 2021. Women with singleton pregnancies, gestational ages between 37 and 42 weeks, and an absence of pregnancy complications were included. In the second trimester, bioelectric impedance analysis (BIA) was used to measure body-composition-related indicators. Logistic regression analysis was performed to explore the risk factors for macrosomia. The predictive performance of maternal body composition and clinical indicators for macrosomia were assessed using the area under the receiver-operating-characteristics curve (AUC). (3) Results: This retrospective study involved 43,020 pregnant women; we collected 2008 cases of macrosomia. Gravidity, gestational age, body mass index (BMI), gestational weight gain (GWG), total body water, fat mass, fat-free mass (FFM), skeletal muscle mass, and visceral fat level were risk factors for macrosomia (p < 0.05 for all). In the prediction model, the AUC of FFM for predicting macrosomia was the largest (0.742). (4) Conclusions: Body-composition-related indicators associated with macrosomia and body composition measurements in the second trimester can predict the risk of macrosomia, enabling clinicians to implement interventions earlier to reduce adverse perinatal outcomes.