Horseweed is an increasingly common and problematic weed in no-till soybean production in the eastern cornbelt due to the frequent occurrence of biotypes resistant to glyphosate. The objective of this study was to determine the influence of crop rotation, winter wheat cover crops (WWCC), residual non-glyphosate herbicides, and preplant application timing on the population dynamics of glyphosate-resistant (GR) horseweed and crop yield. A field study was conducted from 2003 to 2007 in a no-till field located at a site that contained a moderate infestation of GR horseweed (approximately 1 plant m−2). The experiment was a split-plot design with crop rotation (soybean–corn or soybean–soybean) as main plots and management systems as subplots. Management systems were evaluated by quantifying in-field horseweed plant density, seedbank density, and crop yield. Horseweed densities were collected at the time of postemergence applications, 1 mo after postemergence (MAP) applications, and at the time of crop harvest or 4 MAP. Viable seedbank densities were also evaluated from soil samples collected in the fall following seed rain. Soybean–corn crop rotation reduced in-field and seedbank horseweed densities vs. continuous soybean in the third and fourth yr of this experiment. Preplant herbicides applied in the spring were more effective at reducing horseweed plant densities than when applied in the previous fall. Spring-applied, residual herbicide systems were the most effective at reducing season-long in-field horseweed densities and protecting crop yields since the growth habit of horseweed in this region is primarily as a summer annual. Management systems also influenced the GR and glyphosate-susceptible (GS) biotype population structure after 4 yr of management. The most dramatic shift was from the initial GR : GS ratio of 3 : 1 to a ratio of 1 : 6 after 4 yr of residual preplant herbicide use followed by non-glyphosate postemergence herbicides.