Narrow row spacing and layered residual herbicides are recommended for season-long control of herbicide-resistant weeds, but limited research is available to describe interactions between the two practices. The integration of narrow row spacing with layered residual herbicides in herbicide-resistant soybean was evaluated in four site-years. A split-split plot treatment arrangement where the whole plot was soybean trait (LLGT27 or EnlistE3), the subplot was row spacing (38 or 76 cm), and the sub-subplot factor was herbicide program with five treatments: nontreated, preemergence herbicide only (PRE), PRE followed by postemergence (PRE fb POST), PRE fb POST with overlapping residual herbicide (POR), and weed free. Weed control was evaluated through R7 soybean, and weed biomass was collected before POST applications and at R7 soybean. Soybean yield was recorded. Data were subjected to analysis of variance and means separation (α = 0.05). Row spacing had minimal effects on weed control and mixed effects on yield. Waterhemp and Venice mallow control ranged from 83% to 100% 4 weeks after treatment (WAT). POST and POR treatments provided ≥ 94% control of Palmer amaranth 4 WAT; however, PRE resulted in 33% Palmer amaranth control. All treatments resulted in ≥ 95% Palmer amaranth and yellow foxtail control at Scandia during 2021. The greatest income in rainfed site-years was Enlist soybean planted in 76-cm rows with PRE herbicide treatment. The greatest income in the irrigated site-year was with Enlist soybean planted in 38-cm rows with PRE herbicide treatment. Both POST and POR increase weed control compared to PRE, regardless of row spacing in the soybean varieties evaluated, although POR resulted in less income than POST treatments. However, this research did not evaluate weed seed production, which is crucial for long-term weed management and profitability.