Proper N management in upland cotton (Gossypium hirsutum L.) is essential to optimize yields. Information on proper N application rate and placement method is needed for coarse-textured soils of the humid Southeast. The objective of this study was to measure strip-tilled cotton performance in response to five N rate and placement application methods. Five N rates (0, 45, 90, 135, and 180 kg N ha −1) and three placement methods {broadcast (urea + ammonium sulfate [AMS], surface banded (urea ammonium nitrate [UAN] + ammonium thiosulfate [ATS]), and injected (UAN + ATS) were evaluated from 2016 to 2018 at five sites in Virginia and one site in North Carolina. Petiole NO 3-N, lint yield, lint percent turnout, and fiber quality parameters were measured. Nitrogen rate and placement had a significant effect on lint yield but only N rate affected petiole NO 3-N concentration. Quadratic plateau analysis of relative yield found that 133, 128, and 180 kg N ha −1 were the optimum N rates for injected, surface-banded, and broadcast systems with relative yields of 95, 90, and 94%, respectively. A critical petiole NO 3-N concentration threshold of 5600 mg NO 3-N kg −1 at early bloom was calculated to reach 92% relative yield. Neither rate nor placement had an effect on fiber quality parameters. This study shows that both surface banding and injecting between 128 and 133 kg N ha −1 can produce 90% or more relative yield for a modern cotton variety in the upper southeastern coastal plain of the United States.