Background <p>The synergistic impact of isolate maternal hypothyroxinaemia (IMH) and other modulators on fetal growth outcomes is unknown. This study was aimed to determine whether third trimester IMH [free thyroxine level (FT4) below the the 5th percentile and thyroid stimulating hormone (TSH) between the 5th and 95th percentiles] and prenatal body mass index (BMI) jointly increase the risk of large for gestational age (LGA) deliveries.</p> Methods <p>A retrospective analysis was conducted on 11,478 Chinese pregnant women with laboratory data (including thyroid hormone levels and routine biochemical tests) and hospitalization records from a specialized hospital.</p> Results <p>The prevalence of obesity (BMI ≥ 30&#xa0;kg/m²) and IMH was 20.1% (2312/11478) and 4.5% (519/11478), retrospectively. Women with obesity had a 6.96-fold greater risk of IMH (95% CI: 4.58, 10.58) and a 5.88-fold increased risk of LGA (95% CI: 4.87, 7.11) than those with normal weight (BMI &lt; 25&#xa0;kg/m²), while women with IMH had a 1.32-fold increased risk of LGA (95% CI: 1.05, 1.65) than euthyroid women. The positive associations of LGA risk with obesity and IMH remained robust in sensitivity analyses conducted among women aged &lt; 35 years, primiparas, and those without pregnancy complications. Compared to euthyroid women with normal weight, women with obesity and IMH had a 7.60-fold higher risk of LGA (95% CI: 5.26, 10.97). Additionally, a significant interaction between BMI categories and IMH on LGA was observed (<i>P</i> &lt; 0.013). Subgroup analyses validated this interaction among women with aged &lt; 35 years, multiparity, and non-pregnancy complications.</p> Conclusions <p>Obesity and IMH in late pregnancy are both associated with an increased risk of LGA newborns, and their coexistence may further amplifies this risk; prenatal BMI and thyroid hormone levels could serve as potential indicators for identifying individuals at elevated LGA risk.</p>