Abstract Monitoring herbicide-resistant weeds makes it possible to study the evolution and spread of resistance, which provides important information for their management. The objective of this study was to map fleabane accessions in the states of Paraná (PR) and Mato Grosso do Sul (MS), Brazil, to identify herbicide-resistant accessions and their response to soybean preplant chemical burndown management strategies. Fleabane seeds were collected in agricultural areas in PR and MS in 2018, 2019, and 2020. Initial screening was performed for glyphosate, chlorimuron, paraquat, 2,4-D, saflufenacil, and glufosinate efficacy. Subsequently, dose-response experiments were conducted. Field experiments were carried out in three locations, where accessions of multiple herbicide–resistant Sumatran fleabane were identified. Herbicides were used in single or sequential applications at three plant heights (<5 cm, 5 to 10 cm, and >10 cm). After preliminary screening, accessions were classified as putative resistant (<80% control for all four replicates), segregated (<80% control for one to three replicates), or susceptible (>80% control for all four replicates). There was no evidence of resistance to glufosinate or saflufenacil in any of the 461 accessions, while 65 demonstrated possible resistance or segregation to glyphosate only, 235 to glyphosate + chlorimuron, 79 to glyphosate + chlorimuron + paraquat, 59 to glyphosate + chlorimuron + 2,4-D, and 23 with four-way resistance (glyphosate, chlorimuron, paraquat, and 2,4-D). Of these 23 accessions, seven were analyzed using dose-response curves (F2 generation), all from PR, confirming four-way resistance to glyphosate, chlorimuron, paraquat, and 2,4-D. To control resistant Sumatran fleabane, an application should prioritize smaller plants. Despite resistance to 2,4-D, double mixtures containing this herbicide were among the most effective treatments in plants <5 cm in height. If a sequential application is needed for plants >5 cm in height, we recommend glyphosate + synthetic auxin followed by glufosinate or glyphosate + saflufenacil.