Promoting sustainable agriculture in the semi-arid, rainfed areas of Central Spain requires understanding how weed population respond to different cropping systems and evaluating their economic profitability. A six-year field experiment compared three systems: a no-till barley (Hordeum vulgare L.) monoculture with fertilizers and herbicides (NT); a two-year rotation of grain legume or false flax [Camelina sativa (L.) Crantz] followed by barley, with reduced tillage and agrochemicals (MW); and a three-year fallow–grain legume–barley rotation under organic practices (ORG). Results showed that NT consistently provided the most effective weed control, reducing total weed density by 79–84% compared to ORG over the last three years of the study. MW also significantly reduced total weed density by 11–75% relative to ORG, though some species increased. ORG was the least effective system, with weed densities reaching 395 plants m-2 and the lowest control efficacy. Weed population dynamics varied by management. Rigid ryegrass (Lolium rigidum Gaudin) was effectively controlled in NT through a consistent annual herbicide program and in MW by combining periodic tillage with targeted herbicide applications; however, it was extremely difficult to manage in ORG. Corn poppy (Papaver rhoeas L.) increased over time in all systems, while other species showed no clear trends. Weed species diversity was lowest in NT, with mean species richness reduced by 34–39% compared to ORG and by 13–17% compared to MW. Economic analysis revealed the highest adjusted net returns in MW and the lowest in ORG, driven by differences in crop sequences, yields, and subsidies from the European Common Agricultural Policy. These findings offer valuable insights for optimizing weed management in rainfed cereal systems, highlighting the importance of integrated approaches that balance effective weed control, crop productivity and economic viability.