Food production is crucial for national stability and the well-being of the population. As the "ballast" for ensuring stable food production and supply, major grain-producing areas play a vital role in safeguarding national food security. While academia has extensively studied the relationship between grain production and economic development in the major grain-producing areas, there is a dearth of research focusing on the interplay among grain production, economic development, and ecological protection. This study utilizes data on grain production, socioeconomic, ecological protection, and natural endowments from 1,265 counties in major grain-producing areas from 2000 to 2020. Employing spatial analysis techniques, the coupling coordination degree model, and the geographical detector model, this study systematically analyzes the spatiotemporal evolution characteristics of grain production, economic development, and ecological protection in these areas. It further explores the spatiotemporal coupling patterns of the grain-economic-ecological system and identifies its primary driving forces. Results show that over the past 20 years, significant progress has been made in grain production, economic development, and ecological protection in major grain-producing areas. However, during the latter decade, the growth rates of grain production and economic development slowed, and some regions have experienced ecological degradation. Approximately 75% of counties in these areas showed an increasing trend in grain production, 78% exhibited an upward trend in the Normalized Difference Vegetation Index (NDVI), and GDP rising in almost all counties. Grain production in major grain-producing areas shows a spatial pattern of being high in the three northeastern provinces and central traditional agricultural areas and low in the western regions. Over the past two decades, the grain production center of the major grain-producing areas has shifted 288 kilometers to the northeast. Economic development levels decrease gradually from east to west, while NDVI displays a "high in the south and east, low in the north and west" distribution pattern. The coupling coordination degree of the grain-economic-ecological system in major grain-producing areas has continuously improved during the study period but has declined in the past five years. The coupling coordination relationship of the grain-economic-ecological system in major grain-producing areas is influenced by multiple factors, with the interaction driving force of two factors being greater than the effect of a single factor. The primary type of interaction is nonlinear enhancement of two factors, indicating that these areas have long faced the challenge of balancing grain production, economic development, and ecological protection. These findings can provide theoretical basis and practical support for national food security strategies and rural revitalization strategy decision-making.