Wheat cultivars with low cadmium (Cd) accumulation (WCCA-Cd) are widely used on Cd-contaminated farmland and can effectively reduce the grains Cd content to achieve the clean production in agriculture. However, there is a lack of soil Cd content thresholds specifically for the WCCA-Cd. To achieve safer production of wheat grains, a prediction model for WCCA-Cd was developed based on total Cd content in wheat grains (Grain-Cd) and soil factors using 379 soil‒wheat datasets from 10 field experiments in this research. The adaptability of the prediction model was tested using 312 pairs of data. Descriptive statistics (N = 379) showed that soil pH ranged from 4.28 to 8.76, the total Cd content in soil (Soil-Cd) ranged from 0.09 to 10.25 mg kg−1, and Grain-Cd ranged from 0.002 to 1.35 mg kg−1. Correlation analysis showed that Grain-Cd had a highly significant negative correlation with soil organic matter (SOM), soil pH, and soil conductivity (EC) and a highly significant positive correlation with Soil-Cd and Cd content in the diethylenetriaminepentaacetic acid extraction state (DTPA-Cd) (P < 0.001). The bioconcentration factor (BCF) decreased with increaseing soil pH. Both random forest and stepwise regression equations indicated that the most important factors affecting Cd bioeffectiveness were Soil-Cd and soil pH, explaining 80% of the variation in Grain-Cd. The prediction model indicated a soil Cd threshold (0.23–1.25 mg kg−1) for the safe production of WCCA-Cd at soil pH (4–9), which has a wider range of applicability compared with the Chinese Soil Safety Standards. Therefore, these results can quantify the grain Cd content of WCCA-Cd and guide the safe and clean production of WCCA-Cd on different Cd contaminated farmlands.