Field experiments were conducted in 2012 and 2013 to determine the effects of row spacing, seeding rate, and herbicide programs on multiple-resistant waterhemp control and yield in glufosinate-resistant soybean. The two herbicide programs evaluated were: (1) a PRE application of fomesafen plus S-metolachlor followed by early POST application of glufosinate plus acetochlor, referred to as the PRE followed by (fb) POST with residual (w/RES) herbicide program; and (2) an early POST followed by a late POST application of glufosinate, referred to as the two-pass POST herbicide program. Results indicate that the PRE fb POST w/RES program provides greater control of resistant waterhemp compared to the two-pass POST herbicide program. In 2012, the PRE fb POST w/RES program resulted in a 99% waterhemp density reduction and 156 kg ha−1 increase in yield compared to the 72% density reduction by the two-pass POST program. In 2013, the two-pass POST program was equally as effective on density reduction and yield as the PRE fb POST w/RES program. Waterhemp control and density reduction was always greatest with 19- and 38- compared to 76-cm rows. In 2012, the PRE fb POST w/RES program provided at least 95% control and greater than 98% density reduction across all row spacings, whereas the two-pass POST program provided 95%, 95%, and 85% control and 87%, 80%, and 50% density reduction in 19-, 38-, and 76-cm rows, respectively. Soybean seeding rate did not affect waterhemp control or density in either year. In both years, 165,000 seeds ha−1 yielded lower than the three higher seeding rates. Overall, results from these experiments indicates that the use of a PRE fb POST w/RES program, narrow-row spacing, and seeding rates of 240,000 to 315,000 seeds ha−1 or greater provides the greatest waterhemp control, density reduction, and soybean yield when multiple resistant waterhemp is present.