Rising herbicide use in the cereal-growing zones of western Burkina Faso has raised concerns about soil contamination and associated ecotoxicological risks. This study assesses soil contamination by thirteen herbicides commonly used in cereal cultivation across twelve localities in four regions of western Burkina Faso during a single agricultural season. Soil samples were collected in two phases: the first during herbicide applications and the second three months later. Residues were extracted using an adapted QuEChERS method and quantified by high-performance liquid chromatography (HPLC). Results indicate spatiotemporally heterogeneous contamination, with maximum concentrations reaching 6,967 µg/kg for nicosulfuron and 1,027 µg/kg for mesotrione. Comparison with maximum allowable concentrations / predicted no-effect concentrations for soil (MAC/PNEC_soil) shows notable exceedances by factors of 10–700—signaling high risk for soil organisms and sensitive crops. Certain compounds, such as atrazine, terbuthylazine and bensulfuron-methyl, exhibit high persistence, whereas others, including nicosulfuron and prometryn, dissipate more rapidly. These findings underscore the urgency of tighter stewardship of phytosanitary practices, the implementation of sustainable management measures, and the integration of international benchmark thresholds into agricultural soil monitoring frameworks.