Zinc (Zn)-biofortified wheat may contribute to decreasing widespread human Zn deficiency. Such genotypes may also accumulate cadmium (Cd) in grains that would expect to be decreased by Zn application. However, the influence of soil and foliar Zn application on grain Cd accumulation in Zn-biofortified versus standard wheat is unknown. In our experiment, we grew standard (Faisalabad-2008) and Zn-biofortified (Zincol-2016) wheats in pots having uncontaminated (T0) or Cd-spiked (8 mg kg−1) soil. Plants in Cd-amended pots were treated with no Zn (T1), 8 mg Zn kg−1 to soil at sowing (T2), 0.5% w/v ZnSO4·7H2O to foliage at booting and heading (T3), or soil (as in T2) + foliar (as in T3) Zn application (T4). Only in the uncontaminated control, grain yield of Faisalabad-2008 was greater than Zincol-2016. Any Zn application to Zincol-2016 grown in Cd-spiked pots increased grain yield compared with the uncontaminated control. In both cultivars, grain Zn concentration was influenced more by foliar than soil Zn application. However, Zincol-2016 had 6 to 14 mg more Zn kg−1 in grains than Faisalabad-2008 in the comparable treatments. Cadmium exposure (T1 vs. T0) decreased grain yield of only Faisalabad-2008, and decreased grain Zn concentration only in Zincol-2016. Without any Zn application, grain Cd concentration in both cultivars exposed to Cd was above the permissible level (0.20 mg kg−1). Zinc application decreased grain Cd concentration, although it remained above the permissible level in both cultivars except in Faisalabad-2008 when treated with soil + foliar Zn. Foliar Zn application decreased grain Cd concentration more than soil Zn application, and more in Zincol-2016 than Faisalabad-2008. In the comparable Cd-spiked treatments, Zincol-2016 had 73 to 134% higher grain Cd concentration than Faisalabad-2008. The Zn-biofortified genotypes accumulating toxic metals may pose serious health issues. Therefore, future breeding for biofortification should focus on the selective accumulation of Zn.