Often obscured in the history of the nineteenth-century US-Mexico borderlands, European-born entrepreneurs played a definitive role in pushing the Rio Grande borderlands into Atlantic markets. These borderlands entrepreneurs tried to transform the Lower Rio Grande and its surroundings from a regional crossroads of trade to a hub of the Atlantic economy. Though they were often stymied by mismanagement, notions of ethnic and cultural superiority, and eruptions of violence, these entrepreneurs persistently attempted to remake the region into a modern commercial utopia. Their actions challenged United States imperial expansion into the Rio Grande borderlands as they tried to modernize the region according to European cultural precepts through constructing colonies populated with Europeans, building strong networks of local and global significance, and striving to dominate trade in the region. Globalizing the Lower Rio Grande reframes the narrative of the borderlands through the perspectives of Europeans who actively shaped the historical trajectory of the region. It highlights the actions of folks like English-born John C. Beales, who convinced a party of Europeans to trek overseas and overland to the isolated Las Moras Creek to build a colony from scratch; Alexander Bourgeois d’Orvanne, former mayor of Clichy-la-Garenne in France, who manipulated powerful French and German leaders to support a settlement scheme on the Rio Grande; Spanish-born José San Román and the way he constructed massive transatlantic networks of credit and exchange; and Joseph Kleiber from Strasbourg, who facilitated the construction of a European-owned railroad line along the Rio Grande. Though ultimately undermined and outmaneuvered by their American rivals, European-born borderlands entrepreneurs like these collectively globalized the Lower Rio Grande.