Entrepreneurship has been a basic element of Latinx life in the United States since long before the nation’s founding, varying in scale and cutting across race, class, and gender to different degrees. Indigenous forms of commerce pre-dated Spanish contact in the Americas and continued thereafter. Beginning in the 16th century, the raising, trading, and production of cattle and cattle-related products became foundational to Spanish, Mexican, and later American Southwest society and culture. By the 19th century, Latinxs in US metropolitan areas began to establish enterprises in the form of storefronts, warehouses, factories, as well as smaller ventures including peddling. At times, they succeeded previous ethnic owners; in other moments, they established new businesses that shaped everyday life and politics of their respective communities. Whatever the scale of their ventures, Latinx business owners continued to capitalize on the migration of Latinx people to the United States from Latin America and the Caribbean during the 20th century. These entrepreneurs entered business for different reasons, often responding to restricted or constrained labor options, though many sought the flexibility that entrepreneurship offered. Despite an increasing association between Latinx people and entrepreneurship, profits from Latinx ventures produced uneven results during the second half of the 20th century. For some, finance and business ownership has generated immense wealth and political influence. For others at the margins of society, it has remained a tool for achieving sustenance amid the variability of a racially stratified labor market. No monolithic account can wholly capture the vastness and complexity of Latinx economic activity. Latinx business and entrepreneurship remains a vital piece of the place-making and politics of the US Latinx population. This article provides an overview of major trends and pivotal moments in its rich history.