A soybean trait resistant to sulfonylurea herbicides along with glyphosate (Bolt™ soybean) has been developed. Information is needed to determine herbicide programs for weed control and crop safety in this new multiple herbicide–resistant soybean trait. The objectives of this study were to evaluate weed control and crop safety in sulfonylurea/glyphosate-resistant soybean with herbicide programs, including but not limited to acetolactate synthase (ALS) inhibitors. Field experiments were conducted near Clay Center, NE, USA, in 2016 and 2017. Herbicide programs with multiple sites-of-action including rimsulfuron/thifensulfuron in mixture with flumioxazin, flumioxazin/chlorimuron, pyroxasulfone, chlorimuron/metribuzin, or saflufenacil/imazethapyr plus dimethenamid-P provided 91%–97% control of common waterhemp, velvetleaf, and common lambsquarters. Rimsulfuron and (or) thifensulfuron resulted in 92%–97% control of velvetleaf and common lambsquarters and 81%–87% common waterhemp control at 21 d after pre-emergence (PRE) (DAPRE) herbicide application. Soybean injury was transient and varied from 3% to 11% at 21 DAPRE and 14 d after post-emergence (POST) (DAPOST) herbicide application without causing yield loss. At 30 and 60 DAPOST, 87%–97% velvetleaf control and 92%–98% common lambsquarters control was achieved with herbicide programs tested (PRE, POST, or PRE followed by POST). Common waterhemp control at 30 and 60 DAPOST was not consistent between years. Weed density and biomass reduction were mostly similar to weed control achieved. Untreated control resulted in the lowest soybean yield (1811 kg ha⁻¹) in 2016 compared with 3406–4611 kg ha⁻¹ in herbicide programs.