Rapid infant weight gain predicts childhood obesity. We aimed to estimate effect size and identify critical timing for intervention-assisted smoking cessation during pregnancy to impact infant weight gain. We followed 25 mother-infant dyads in the UB Pregnancy and Smoking Cessation Study (Buffalo, NY, USA). Maternal smoking status was biochemically verified and monitored through pregnancy. Birth weight and length were extracted from birth records. Research staff measured infant weight and length at 2 weeks and monthly from 1 to 12 months of age. Mixed models were used to fit infant BMI-for-age z-score (ZBMI) trajectories. We found infants of quitters had lower ZBMI gain from birth to 12 months (mean ± SD, 1.13 ± 1.16) than infants of persistent smokers (2.34 ± 1.40; p = 0.035), with Cohen's d effect size being large (0.96). The infant ZBMI gain from birth to 12 months was low (<0.47) if smoking cessation was initiated between 15 and 27 weeks of pregnancy, but started to increase if quitting at 28 weeks (0.65) and accelerated with time (e.g., 3.16 if quitting at 36 weeks). We concluded maternal smoking cessation during pregnancy may reduce fetal origins of obesity through reducing infant weight gain, especially if quitting smoking by 27 weeks of pregnancy.