Mesoamerica is one of the world’s primary centers of domestication where agriculture arose independently. Paleoethnobotany (or archaeobotany), along with archaeology, epigraphy, and ethnohistorical and ethnobotanical data, provide increasingly important insights into the ancient agriculture of Lowland Mesoamerica (below 1000 m above sea level). Moreover, new advances in the analysis of microbotanical remains in the form of pollen, phytoliths, and starch-grain analysis and chemical analysis of organic residues have further contributed to our understanding of ancient plant use in this region. Prehistoric and traditional agriculture in the lowlands of Mesoamerica—notably the Maya lowlands, the Gulf Coast, and the Pacific Coast of southern Chiapas (Mexico) and Guatemala—from the Archaic (ca. 8000/7000–2000 bc) through the Preclassic/Formative (2000 bc–ad 250) and into the Classic (ad 250–900) period, are covered. During the late Archaic, these lowland regions were inhabited by people who took full advantage of the rich natural biodiversity but also grew domesticates before becoming fully sedentary. Through time, they developed diverse management strategies to produce food, from the forest management system (which includes swidden agriculture), to larger scale land modifications such as terraces, and continued to rely on semidomesticated and wild plant resources. Although lowland populations came to eventually rely on maize as a staple, other resources such as root crops and fruit trees were also cultivated, encouraged, and consumed. The need for additional research that includes systematic collection of paleoethnobotanical data, along with other lines of evidence, will be key to continue refining the understanding of ancient subsistence systems and how these changed through time and across lowland Mesoamerica.