| Crop nutrient requirements vary in sole/mono and multiple cropping systems indicating the need for optimization of fertilization programs. This 2-years study was performed to investigate the influence of different strategies related to NPK fertilization timing viz. T1 (control, no NPK application), T2 (all PK at sowing, ½ N at tillering and ½ at booting), T3 (½ PK at sowing, ½ NPK at tillering and ½ N at booting), T4 (all PK at sowing, ½ N at sowing and ½ at tillering), T5 (all PK at tillering, ½ N at tillering and ½ at booting), T6 (all PK at tillering and N at booting) and T7 (all NPK at sowing) on growth, yield, agronomic nutrient use efficiency of nitrogen (NUEA) and economic benefits of relay-intercropped wheat in cotton. Fertilization timing significantly affected growth, yield and NUEA of wheat. Application of T4 (all PK at sowing, ½ N at sowing and ½ at tillering) caused maximum improvement in plant height, fertile tillers, grains per spike, biological yield, grain yield and NUEA. Economic analysis also manifested that the greatest net returns and benefit cost ratio (BCR) were obtained by same NPK application timing (i.e. T4). In conclusion, fertilization timing substantially affected the yield, NUEA and economic benefits of relay intercropped wheat in cotton; and application of ½ N and all PK at sowing and ½ N at tillering was most appropriate option.