Pot trials were performed to explore the impacts of seed priming (SPr) plus leaf treatment (LTr) with trans-zeatin-type cytokinin (tZck; 0.05 mM) and silymarin (Sim; 0.5 mM) on growth, yield, physio-biochemical responses, and antioxidant defense systems in Cd-stressed wheat. tZck + Sim applied as SPr + LTr was more effective than individual treatments, and the impacts were more pronounced under stress conditions. Cd stress (0.6 mM) severely declined growth and yield traits, and photosynthesis efficiency (pigment contents, instantaneous carboxylation efficiency, and photochemical activity) compared to the control. These negative impacts coincided with increased levels of Cd2+, O2•− (superoxide), H2O2 (hydrogen peroxide), MDA (malondialdehyde), and EL (electrolyte leakage). Non-enzymatic and enzymatic antioxidant activities, and tZck and Sim contents were also increased. However, tZck + Sim increased photosynthesis efficiency, and further boosted antioxidant activities, and contents of tZck and Sim, while minimizing Cd2+ levels in roots, leaves, and grains. The levels of O2•−, H2O2, MDA, and EL were also minimized, reflecting positively on growth and productivity. tZck + Sim applied as SPr + LTr was highly effective in promoting antioxidants and photosynthesis machineries, minimizing oxidative stress biomarkers and Cd2+ levels, boosting tolerance to Cd stress, and improving wheat productivity under Cd stress.