The growth and productivity of wheat crops depend on the availability of essential nutrients such as zinc (Zn) and potassium (K2O), which play critical roles in the plant’s physiological and biochemical processes. This study aimed to investigate the synergizing effect of zinc and potassium fertilizers on uptake of both the nutrients, growth, yield, and quality of the Hashim-08 cultivar and local landrace, during the 2019–2020 growing season in Dera Ismail Khan, Pakistan. The experiment was designed using a split plot pattern in a randomized complete pattern, with main plots for the wheat cultivars and subplots for the fertilizer treatments. Results indicated that both cultivars responded positively to the fertilizer treatments, with the local landrace exhibiting maximum plant height and biological yield, and improved Hashim-08, showing increased agronomic parameters, including the number of tillers and grains and spike length. Application of Zn and K2O fertilizers significantly enhanced agronomic parameters, such as the number of grains per plant, spike length, thousand-grain weight, grain yield, harvest index, Zn uptake of grain, dry gluten content, and grain moisture content, while crude protein and grain potassium remained relatively unchanged. The soil’s Zn and K content dynamics were found to vary among treatments. In conclusion, the combined application of Zn and K2O fertilizers proved beneficial in improving the growth, yield, and quality of wheat crops, with the local landrace exhibiting lower grain yield but greater Zn uptake through fertilizer application. The study’s findings highlight that the local landrace showed good response to the growth and qualitative parameter when compared with the Hashim-08 cultivar. Additionally, the combined application of Zn and K showed a positive relation in terms of nutrient uptake and soil Zn and K content.