In this article, we comprehensively review Agave maximiliana, a plant endemic to western Mexico, addressing its history, biology, genetics, economics, and relevance in the production of the ancestral “mezcal wine” or raicilla. This agave stands out for its cultural, economic, and ecological value, being a multifunctional source of fiber, food, and beverages. Historically, its use dates back to pre-Hispanic and colonial practices. From a biological perspective, A. maximiliana presents high morphological variability and ecological adaptations that allow it to thrive in extreme conditions. Genetic studies have revealed low genetic diversity, attributed to the low efficiency of pollinators and the pressure of their exploitation for raicilla. However, integrated agroforestry systems offer a solution for its conservation. The review also examines biotechnological applications, including micropropagation protocols to mitigate the overexploitation of wild populations and promote sustainable cultivation. The common ancestor of all mezcals, called “vino mezcal”, emerged in Colima and Jalisco in the 16th century, and from it came famous mezcals such as raicilla, tequila, bacanora, tuxca, and mezcal. The impact of the Denomination of Origin (DO) of raicilla on the sustainability of A. maximiliana is critically analyzed. Although it promotes the authenticity and commercial value of the product, it also generates challenges such as genetic homogenization and pressure on wild populations. The article highlights the need for comprehensive strategies that combine traditional knowledge, technological innovation, and sustainable management to ensure the conservation of this key species and its contribution to ecosystems and the regional economy.