Size-asymmetric competition, in which larger plants obtain a disproportionally larger share of contested resources, can be applied in agriculture to suppress weeds by increasing crop density and spatial uniformity, as these practices enhance the initial size-asymmetric competitive advantages of crop seedlings over weed seedlings early in the growing season. We do not yet know how agronomic factors influence weed suppression at high crop density. We performed a field experiment to ask how crop density, spatial pattern and irrigation interact to influence weed suppression and grain yield in semi-arid croplands. The experimental was a factorial design with 4 factors: wheat cultivar (Ningchun4, Xihan2), irrigation level (control, irrigated), sowing density (low, 196 seeds m⁻²; moderate, 400 seeds m^-2; high, 625 seeds m⁻²), and spatial sowing pattern (rows, uniform). Weed growth was effectively suppressed by increased crop density and spatial uniformity. Effects of crop density on weed suppression and grain yield were more pronounced in the uniform pattern than in crop rows. Weed biomass was 55.7% lower and grain yield increased 29.7% higher in the high density uniform pattern compared to the low density and row pattern. Crop density interacted with cultivar in determining both weed biomass and grain yield, potentially reflecting different traits regulating crop competitive ability. Irrigation and crop density had additive effects on weed biomass but interacted to influence grain yield. Our findings support the idea that increased crop density and spatial uniformity can make a valuable and environmentally friendly contribution to weed control in wheat, reducing the need for chemical or mechanical weed control. We need a better understanding of the interactions among climate, agricultural management and crop genotype to improve our ability to effectively suppress weeds with high crop density and spatial uniformity.