Glyphosate-resistant Palmer amaranth (PA) (Amaranthus palmeri) is a significant issue in agronomic crop production. Research was conducted from 2012 to 2014 and from 2013 to 2015 to quantify the impact of primary tillage, herbicide program, and prevention of PA seed production over a three year cropping sequence of flue-cured tobacco followed by cotton. Treatments imposed to tobacco were deep tillage (15 inch depth) or shallow tillage (5 inch depth), two herbicide programs (clomazone alone or clomazone plus sulfentrazone), and hand removal or no hand removal of PA. In year one, soybean was planted into plots bordering tobacco using deep and shallow tillage treatments to assess early season PA density between cropping systems. Tillage treatments were not imposed in years two or three of the study. Glyphosate and glufosinate were utilized for POST weed suppression in cotton. Weed counts were conducted two and six weeks after crop establishment to assess PA density within each treatment. Palmer amaranth visible above the late season crop canopy was removed in a single event in each year of the study. Hand weeding time was recorded for economic assessment. Crop yield and value were also recorded after harvest. Deep tillage reduced PA density in soybean and tobacco plots compared to shallow tillage; however, PA density was consistently higher in tobacco, most likely due to row ridging. In the absence of sulftentrazone, deep tillage reduced PA density in tobacco two weeks after transplanting but not at six weeks or in subsequent cotton crops. Sulfentrazone reduced PA density and increased tobacco yield and economic return. In the absence of sulfentrazone, hand weeding increased tobacco yield and economic value. Palmer amaranth suppression in cotton was improved in treatments where sulfentrazone and/or hand weeding were utilized in previous season(s). Hand weeding did not affect net economic return. (Reprinted with permission)