Longer duration of breastfeeding is associated with a lower risk of type 2 diabetes, breast and ovarian cancer, myocardial infarction, and hypertension diseases in women. Mexico has one of the lowest breastfeeding rates worldwide; therefore, estimating the disease and economic burden of such rates is needed to influence public policy. We considered suboptimal breastfeeding when fewer than 95% of parous women breastfeed for less than 24 months per child, according to the World Health Organization recommendations. We quantified the lifetime excess cases of maternal health outcomes, premature death, disability-adjusted life years, direct costs, and indirect costs attributable to suboptimal breastfeeding practices from Mexico in 2012. We used a static microsimulation model for a hypothetical cohort of 100,000 Mexican women to estimate the lifetime economic cost and disease burden of type 2 diabetes, breast and ovarian cancer, myocardial infarction, and hypertension in mothers, due to suboptimal breastfeeding, compared with an optimal scenario of 95% of parous women breastfeeding for 24 months. We expressed cost in 2016 USD. We used a 3% discount rate and tested in sensitivity analysis 0% and 5% discount rates. We found that the 2012 suboptimal scenario was associated with 5,344 more cases of all analysed diseases, 1,681 additional premature deaths, 66,873 disability-adjusted life years, and 561.94 million USD for direct and indirect costs over the lifetime of a cohort of 1,116 million Mexican women. Findings suggest that investments in strategies to enable more women to optimally breastfeed could result in important health and cost savings.