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Wheat is an important food crop in China. The quality of wheat affects the development of the agricultural economy. However, the high-quality wheat produced in China cannot meet the demand, so it would be an important direction for research to develop high-quality wheat. Grain protein content (GPC) is an important criterion for the quality of winter wheat and its content directly affects the quality of wheat. Studying the spatial heterogeneity of wheat grain proteins is beneficial to the prediction of wheat quality, and it plays a guiding role in the identification, grading, and processing of wheat quality. Due to the complexity and variability of wheat quality, conventional evaluation methods have shortcomings such as low accuracy and poor applicability. To better predict the GPC, geographically weighted regression (GWR) models, multiple linear regression, random forest (RF), BP neural networks, support vector machine, and long-and-short-term memory algorithms were used to analyze the meteorological data and soil data of Jiangsu Province from March to May in 2019–2022. It was found that the winter wheat GPC rises by 0.17% with every 0.1° increase in north latitude at the county level in Jiangsu. Comparison of the prediction accuracy of the coefficient of determination, mean deviation error, root mean square error, and mean absolute error by analyzing multiple algorithms showed that the GWR model was the most accurate, followed by the RF model. The regression coefficient of precipitation in April showed the smallest range of variation among all factors, indicating that precipitation in April had a more stable effect on GPC in the study area than the other meteorological factors. Therefore, consideration of spatial information might be beneficial in predicting county-level winter wheat GPC. GWR models based on meteorological and soil factors enrich the studies regarding the prediction of wheat GPC based on environmental data. It might be applied to predict winter wheat GPC and improve wheat quality to better guide large-scale production and processing. [ABSTRACT FROM AUTHOR]