Application of N fertilizer and no-tillage (NT) can increase winter wheat (Triticum aestivum L) production through improvements in plant available soil water and nutrient availability. However, long-term tillage and N management interaction effects on winter wheat nutrient uptake are not well known. The objective of this study was to quantify winter wheat grain yield, macronutrient removal, and utilization responses to N fertilizer application and tillage intensity. The study was conducted in 2019 and 2020 at Hays, Kansas after 45 years of tillage and N fertility experiment. Treatments were a combination of two tillage practices (CT, conventional tillage; NT) and four rates of N (0, 45, 90, and 134 kg ha −1 ). Results showed a significant tillage and N fertilizer interaction effect on wheat grain yield, nutrient removal (NR) (grain-N, -P, -K, -Mg; stover-K, and total P), and nutrient concentration (stover-K and -S). Two different quadratic models fit the N rate-to-yield relation for CT and NT with yields of 4.3 and 5.2 Mg ha −1 at agronomic optimal N rates of 119 and 199 kg N ha −1 , respectively. This suggests that the N rates were not high enough to predict optimum N rate for NT in this environment. With an average yield of 3.30 Mg ha −1 , wheat removed about 113 kg N ha −1 , 17 kg P ha −1 , 56 kg K ha −1 , 7 kg Ca ha −1 , 8 kg Mg ha −1 , and 8 kg S ha −1 , irrespective of tillage practice. Grain yields and NR were greater for CT at smaller N rates (<90 kg N ha −1 ) and for NT at greater N rates (>90 kg ha −1 ). Findings of the study suggest that adequate N fertility (>90 kg ha −1 ) should be maintained to improve grain yield, nutrient uptake, and utilization efficiency in dryland NT wheat production systems.