Drought and drought-induced famine are recurring phenomena in Mesoamerica that have devastated populations in the region repeatedly during the past two millennia. Although it is counterintuitive to conceive of the idea that volcanic eruptions anywhere in the world might affect the lives of people in Mesoamerica, we examine the reports of drought and famine during the period A.D. 1440 to 1840 and compare them with known, large volcanic eruptions. We then apply non-parametric statistical techniques to determine whether the coincidences seen between worldwide volcanic eruptions and Mesoamerican drought within the following two years were due to random chance or whether there was a direct, mathematically verifiable correlation. We find a direct correlation to a probability of 56 in 100 million. We conclude that due to its unique geographical position, Mesoamerica was repeatedly devastated by drought and subsequent famine between 1440 and 1840 due to the indirect climatic effects of large volcanic eruptions that could be located anywhere in the world.