No-till cropping is an option for growers needing to reduce soil erosion in the Palouse annual-cropped region of the Pacific Northwest, which is well suited for wheat production. A 6-yr field study was conducted to determine optimum levels of fertilizer and herbicide inputs in a no-till continuous wheat crop production system. Three levels of nitrogen (N) and two weed management levels (WML) were compared in a spring wheat (SW)–winter wheat (WW)–WW rotation through two rotation cycles. The high WML reduced weed densities about 50% compared with the low WML. In general, herbicide treatments were more effective on broadleaf weeds and may have facilitated a shift toward grass weeds. The high WML reduced grass weed biomass only at the reduced N levels, whereas the high WML reduced broadleaf weed density at all N levels. Variable environmental conditions affected wheat yield; however, yield tended to be highest where winter wheat immediately followed spring wheat. Nitrogen had little effect on weed density but increased crop yield about 13% with each increased N level. Crop yield was greater at the high versus low WML at each N level, even though weed density and biomass were reduced least between WMLs at the highest N level. The highest crop yield and net returns were obtained with the highest N and WML; however, none of the N and WML combinations were profitable.