Studies suggest that coincidental adoption of both herbicide-resistant genetically modified crops (GMC) and conservation management may be mutually complementary, but integrated conservation systems with GMCs need to be assessed to balance production goals with environmental concerns. Genetically modified glyphosate-resistant cotton (Gossypium hirsutum L.) was managed on replicated experimental plots as either no-till (NT) or minimum tillage (MT) and with either no cover (NC) or rye (Secale cereal L.) cover crop (CC) from 2001 to 2007 near Stoneville, MS. Rainfall simulations in 2007 were used to evaluate water quality in runoff as influenced by management at two critical times: (i) 24 h after fertilizer application in the spring; and (ii) 24 h after tillage following crop harvest. With the exception of MT-NC in the spring (with the lowest surface plant residue coverage, 2%), runoff was higher in fall than spring. Suspended solids and turbidity in runoff were higher for tilled soil (MT) and areas with no cover crop, particularly in the fall. Tillage in the fall was the largest contributor to erosion loss. Similarly, total orthophosphate and total Kjeldahl N losses were greatest with tillage in the fall, while the lowest dissolved organic C losses in runoff were in fall with NT. Overall, NT and CC treatments reduced nutrient and solids losses. Major factors contributing to these results include recent tillage (in the fall) and coverage of the soil surface by plant residues (NT > MT, CC > NC). This study demonstrated the effectiveness of integrating cover crop and conservation tillage in reducing runoff and nutrient losses in a GMC system. © Soil Science Society of America, 5585 Guilford Rd., Madison WI 53711 USA All rights reserved.