Glyphosate-resistant (GR) horseweed is one of the most common and troublesome weeds in soybean production fields in several states in the United States, including Nebraska. The evolution of horseweed resistant to several herbicide sites of action has prioritized an integrated approach, including tillage, for effective management of this problem weed. The objectives of this study were to evaluate the effect of tillage or herbicide applied in fall or spring followed by a PRE, POST, and PRE followed by a POST herbicide program for GR horseweed control as well as GR soybean injury and yield in Nebraska. Field studies were established in the fall 2014–2015 and 2015–2016 growing seasons using a factorial randomized complete block design with shallow tillage or herbicide applied at different timings as two factors. Shallow tillage was accomplished using a 50-cm-wide rototiller operated at a depth of 10 cm. At soybean harvest, tillage applied the previous year in fall or spring without any follow-up herbicide treatment provided 79% to 88% horseweed control compared with 27% and 56% control with 2,4-D plus carfentrazone applied in fall and spring, respectively. Tillage or herbicide applied in fall or spring followed by a PRE, POST, or PRE and POST herbicide provided 82% to 99% GR horseweed control at soybean harvest. Soybean yield in this study was similar in most treatments. Tillage or herbicide applied in fall or spring provided similar horseweed control and soybean yield when followed by a PRE, POST, or PRE and POST herbicide; therefore, fall- or spring-applied herbicides can be rotated with shallow tillage for integrated season-long horseweed management.