Wheat (Triticum aestivum L.) residues and nitrogen (N) management are the major problems in the southern part of Iran where irrigated wheat-cotton (Gossypium hirsutum L.)-wheat rotation is a common practice. A 2-year (2009-2011) field experiment was conducted as a split plot design with four replications at a cotton field (Darab), Fars Province, Iran, to determine the influence of different rates of wheat residue (0%, 25%, 50%, and 75%) incorporation and N rates (150, 200, 300, and 400 kg ha −1 ) on weed suppression, yield, and yield components of cotton. Results showed that a higher residue incorporation and a lower N rate improved weed suppression in both years. For treatments receiving 150 kg N ha −1 and 75% of wheat residues (2250 kg ha −1 ), weed biomass and density were significantly lower compared to treatments receiving 400 kg N ha −1 . The highest cotton lint yield (about 2400-2700 kg ha −1 ) was obtained by 300 kg N ha −1 in the absence of residue application, in both years. Incorporation of 25% of wheat residue (750 kg ha −1 ) and application of 300 kg N ha −1 are recommended to guarantee an optimum level of cotton lint yield and weed suppression in a wheat-cotton-wheat rotation in this region.