Weed management represents a critical challenge in Sudano-Sahelian agriculture, where environmental constraints and soil fertility limitations create complex weed–crop competition dynamics. This study determined the effects of cropping systems, fertilization modes, and weeding periods on weed diversity, biomass, and ground cover using data from 2018 to 2019. The experiment is being conducted at the Saria Research Station, specifically in Burkina Faso’s only long-term trial (a unique 60-year continuous experiment: 1960–2019). This study used a split-plot design with six fertilization treatments (control, low/high mineral fertilization, organic amendments, and residue incorporation) combined with three crop rotation systems (continuous cropping of sorghum, sorghum–cotton rotation, and sorghum–cowpea rotation). Weed floristic surveys, biomass and ground cover assessments were conducted before and after weeding operations from 2018 to 2019. The study identified 61 weed species across 19 families, with therophytes dominating 75–79% of the flora. Poaceae represented the most diverse family (21 species), followed by Fabaceae (7 species). Species richness varied significantly between years and after weeding (from 7.75 ± 0.41 species per plot to 15.60 ± 0.72 species; p < 0.001). The Shannon index follows the same logic as species richness. In addition, pielou index values were high reflecting sustainable management practices such as crop rotation. Sorghum-cowpea rotation decreased weed cover rate (16.4 ± 2.90%; p < 0.001). After the study, we can state that crop rotation contributes to reducing weed cover rate.