INTRODUCTION: Globalization via free trade and investment agreements is often implicated in the obesity pandemic. Concerns center on how free trade and investment agreements increase population exposure to unhealthy, high-calorie diets, but existing studies preclude causal conclusions. Few studies of free trade and investment agreements and diets isolated their impact from confounding changes, and none examined any effect on caloric intake, despite its critical role in the etiology of obesity. This study addresses these limitations by analyzing a unique natural experiment arising from the exceptional circumstances surrounding the implementation of the 1989 Canada-U.S. Free Trade Agreement. METHODS: Data from the UN (2017) were analyzed using fixed-effects regression models and the synthetic control method to estimate the impact of the Canada-U.S. Free Trade Agreement on calorie availability in Canada, 1978-2006, and coinciding increases in U.S. exports and investment in Canada's food and beverage sector. The impact of changes to calorie availability on body weights was then modeled. RESULTS: Calorie availability increased by ≅170 kilocalories per capita per day in Canada after the Canada-U.S. Free Trade Agreement. There was a coinciding rise in U.S. trade and investment in the Canadian food and beverage sector. This rise in calorie availability is estimated to account for an average weight gain of between 1.8 kg and 12.2 kg in the Canadian population, depending on sex and physical activity levels. CONCLUSIONS: The Canada-U.S. Free Trade Agreement was associated with a substantial rise in calorie availability in Canada. U.S. free trade and investment agreements can contribute to rising obesity and related diseases by pushing up caloric intake.