The La Antigua watershed drains into the Gulf of Mexico and can be considered as one of the most important areas in Mexico because of its high productivity, history, and biodiversity, although poverty remains high in the area in spite of these positive attributes. In this study, we performed an integrated assessment of the watershed to recommend a better direction toward a sustainable management in which the four capitals (natural, human, social, and built) are balanced. We contrasted these four capitals in the municipalities of the upper, middle and lower watershed and found that natural capital (natural ecosystems and ecosystem services) was higher in the upper and middle watershed, while human and social capitals (literacy, health, education and income) were generally higher downstream. Overall, Human Development Index was negatively correlated with the percentage of natural ecosystems in the watershed, especially in the upper and lower watershed regions. Our results indicate that natural capital must be fully considered in projections for increasing human development, so that natural resources can be preserved and managed adequately while sustaining intergenerational well-being.