Introduction This study aimed to summarize the evidence describing the relationship between maternal factors during gestation and risk of congenital heart disease (CHD) in offspring. Methods PubMed, EMBASE, and the Cochrane Library were searched for potentially relevant reports from inception to May 2021. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) calculated by the random-effects model were used to evaluate the association between maternal factors and CHD risk. Results There was a significant association between CHD risk and obesity in pregnancy (OR 1.29, 95% CI 1.22-1.37; P < 0.001), smoking in pregnancy (OR 1.16, 95% CI 1.07-1.25; P < 0.001), maternal diabetes (OR 2.65, 95% CI 2.20-3.19; P < 0.001), and exposure of pregnant women to organic solvents (OR 1.82, 95% CI 1.23-2.70; P = 0.003). No correlations were revealed between CHD susceptibility and advanced maternal age (OR 1.04, 95% CI 0.96-1.12; P = 0.328), underweight (OR 1.02, 95% CI 0.96-1.08; P = 0.519), alcohol intake in pregnancy (OR 1.08, 95% CI 0.95-1.22; P = 0.251), coffee intake (OR 1.18, 95% CI 0.97-1.44; P = 0.105), and exposure to irradiation (OR 1.80, 95% CI 0.85-3.80; P = 0.125). Discussion Maternal factors including maternal obesity, smoking in pregnancy, maternal diabetes and exposure to organic solvents might predispose the offspring to CHD risk.