Ending hunger and alleviating poverty are key goals for a sustainable future. Food security is a constant challenge for agrarian communities in low-income countries, especially in Madagascar. We investigated agricultural practices, household characteristics, and food security in northeast Madagascar. We tested whether agricultural practices, demographics, and socioeconomics in rural populations were related to food security. Over 70% of respondents reported times during the last three years during which food for the household was insufficient, and the most frequently reported cause was small land size (57%). The probability of food insecurity decreased with increasing vanilla yield, rice yield, and land size. There was an interaction effect between land size and household size; larger families with smaller land holdings had higher food insecurity, while larger families with larger land had lower food insecurity. Other socioeconomic and agricultural variables were not significantly related to food insecurity, including material wealth, education, crop diversity, and livestock ownership. Our results highlight the high levels of food insecurity in these communities and point to interventions that would alleviate food stress. In particular, because current crop and livestock diversity were low, agricultural diversification could improve outputs and mitigate food insecurity. Development of sustainable agricultural intensification, including improving rice and vanilla cultivation to raise yields on small land areas, would likely have positive impacts on food security and alleviating poverty. Increasing market access and off-farm income, as well as improving policies related to land tenure could also play valuable roles in mitigating challenges in food security.