Technical Abstract: The tillage-based winter wheat – summer fallow (WW-SF) cropping system has dominated dryland farming in the Pacific Northwest for 125 years. We conducted a large-scale multidisciplinary 8-year study of annual no-till cropping systems as an alternative to WW-SF. Soft white and hard white classes of winter and spring wheat, spring barley, yellow mustard, and safflower were grown in various rotation combinations. Annual precipitation was less than the long-term average of 11.7 inches in 7 out of 8 years. The fungal disease rhizoctonia bare patch appeared in year 3 and continued through year 8 in all no-till plots. All crops were susceptible to rhizoctonia, but bare patch area in wheat was reduced, and grain yield increased, when wheat was grown in rotation with barley every other year. Remnant downy brome weed seeds remained dormant for 6 years and longer to heavily infest recrop winter wheat. There were few quantifiable changes in soil quality due to crop rotation, but soil organic carbon increased in the surface 0-to 2-inch depth with no-till during the 8 years to approach that found in undisturbed native soil. Annual no-till crop rotations experienced lower average profitability and greater income variability compared to WW-SF. Yellow mustard and safflower were not economically viable. Continuous annual cropping using no-till provides excellent protection against wind erosion and shows potential to increase soil quality, but the practice involves high economic risk compared to WW-SF. This comprehensive multidisciplinary report illustrates long-term alternative annual no-till cropping systems research in the low-precipitation region of the Pacific Northwest.