Wheat (Triticum aestivum L.) is a major food source supplying nutrients required for adequate human nutrition. Changing fertility and cropping practices could alter the concentration of essential elements in wheat grain. This study utilized two long-term field experiments to determine the effect of nitrogen (N) and phosphorus (P) fertilization and cropping system on the concentration of N, P, potassium (K), sulphur (S), calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), and zinc (Zn) in wheat grain. Fertilizer P increased P (18%), K (6%), Mg (4%), and Mn (7%) concentrations but decreased Zn (26%) and Cu (22%). The grain concentration of P, K, Ca, Mg, Mn, and Zn declined as crop yields increased in response to N fertilization or more favourable growing conditions. A cropping system with alfalfa hay increased the wheat grain concentration of N (10%), S (17%), Cu (20%), Mg (18%), and Zn (50%). Cropping systems with wheat alone had only minor effects on human nutrient concentrations in wheat grain, depending on the frequency of fallow. Changing wheat production systems, especially fertilizer application, could suppress the availability of essential micronutrients Cu and Zn if the concentrations were already low but most other elements were generally adequate.