Interactions between climate change and anthropogenic activities result in increasing numbers of open fires, which have been shown to harm maternal health. However, few studies have examined the association between open fire and pregnancy loss. We conduct a self-comparison case-control study including 24,876 mothers from South Asia, the region with the heaviest pregnancy-loss burden in the world. Exposure is assessed using a chemical transport model as the concentrations of fire-sourced PM2.5 (i.e., fire PM2.5). The adjusted odds ratio (OR) of pregnancy loss for a 1-μg/m3 increment in averaged concentration of fire PM2.5 during pregnancy is estimated as 1.051 (95% confidence intervals [CI]: 1.035, 1.067). Because fire PM2.5 is more strongly linked with pregnancy loss than non-fire PM2.5 (OR: 1.014; 95% CI: 1.011, 1.016), it contributes to a non-neglectable fraction (13%) of PM2.5-associated pregnancy loss. Here, we show maternal health is threaten by gestational exposure to fire smoke in South Asia.