Wheat is the second most important staple food crop, therefore safe and environmentally friendly production of wheat is essential for human safety and health. Southern Jiangsu province is a very important wheat producing region that is highly industrialized with many soils polluted with potentially toxic metals, especially cadmium (Cd). Wheat varieties with low Cd bioconcentration factors (BCF) are often used to decrease Cd accumulation and increase the safety of products in field practice. In addition, the development of local soil safety thresholds, the main focus of soil health management, is also necessary to protect agricultural soil health and agricultural production. However, there is no published literature describing low-Cd-accumulating wheat varieties and soil safety thresholds in this region. Field plot experiments and field investigations at multiple experimental sites in southern Jiangsu province have therefore been conducted for several years to screen low-Cd-accumulating wheat varieties and to derive soil Cd safety thresholds. The varieties Yangmai 25, Zhengmai 12 and Yangmai 12 had stable and low Cd BCF. The deduced safe thresholds of total soil Cd concentrations for protecting 95 % of wheat varieties were 0.17, 0.18, and 0.31 mg kg−1 at 4.5 < pH ≤ 6.5, 6.5 < pH ≤ 7.5 and 7.5 < pH ≤ 9.0, stricter levels than the Chinese national risk screening values. The deduced thresholds were validated to increase the protection rates of wheat by field investigations. In conclusion, wheat varieties with low Cd BCF and soil thresholds can contribute to local soil health management and safe wheat production in southern Jiangsu province.