Residues retention in zero tillage (ZT) system is a highly resourceful mean of managing nitrogenous fertilizers and optimizing the nitrogen (N) use efficiencies, lint yield and fiber quality in wheat-cotton system. Therefore, a field experiment was conducted during 2014, 2015 and 2016 at Cotton Research Station, Dera Ismail Khan, Pakistan to explore N management practices for ZT cotton grown into standing wheat straw. The trial was conducted in a randomized complete block (RCB) design with three replications. Results showed that cotton lint yield and fiber quality was good during 2016 than that in 2014 and 2015. Ammonia volatilization loss from urea broadcast over the residue covered surface, followed by irrigation, was low (<2 kg ha−1) regardless of time of urea application. N treatments significantly affected the N uptake, N use efficiencies, lint yield and fiber quality traits. Drilling of 24 kg N ha−1 as DAP into soil at cotton seeding followed by three top-dressing of 42 kg N ha−1 each just prior to first, second and third irrigations significantly enhanced seed cotton yield, quality, N uptake and N efficiencies compared to conventional practices. In conclusion, drilling of 24 kg N ha−1 as DAP into the soil at cotton sowing followed by three top-dressing of 42 kg N ha−1 each just prior to first, second and third irrigations is a better applied N management strategy for ZT cotton that enhanced cotton yield, quality and N efficiency in wheat-cotton system.