BACKGROUNDRaphanus raphanistrum causes $40 million total revenue losses annually in Western Australia partly due to its historically‐documented ability to evolve herbicide resistance to multiple modes of action. In this study, 376 field‐sampled populations of R. raphanistrum were tested for resistance to 21 herbicides applied at the recommended label rate. Eight treatments were herbicide mixtures with two, three or four modes of action.RESULTSA total of 7199 individual resistance tests were conducted across 4 years by screening approximately 104 000 individual seeds and seedlings. The mean survival of individuals within a population for all standalone herbicides was 9%, whereas survival was significantly decreased to 3.5% with a herbicide mixture. Some herbicides such as triasulfuron (herbicide Group 2), 2,4‐D (Group 4) or diflufenican (Group 12) were highly impacted by resistance, with frequencies of resistant populations being > 50%. Conversely, there was negligible resistance to glyphosate (Group 9) or protoporphyrinogen oxidase (PPO) inhibitors (tiafenacil, saflufenacil + trifludimoxazin, fomesafen: Group 14), and pre‐emergence herbicides (i.e., atrazine or mesotrione: Groups 5 and 27, respectively) remained largely effective. Binary, ternary or quaternary mixtures of Groups 4, 6, 12 and 27 herbicides reduced the frequency of high‐level resistant populations to 7.1%, 3.8% or 0%, respectively.CONCLUSIONSThe cost‐effective control of R. raphanistrum remains a challenge due to herbicide resistance. Raphanus raphanistrum management relies heavily on herbicide uses not yet compromised by resistance, such as pre‐emergence herbicides (atrazine, fomesafen, mesotrione), glyphosate, and mixtures of two, three or four modes of action including bromoxynil, diflufenican, MCPA, picolinafen, pyrasulfotole and topramezone. Strategies that integrate effective herbicide use patterns, novel modes of action and efficiently‐mechanized non‐chemical weed control options (i.e., seed destructors) can completely constrain the selection of herbicide resistance in this highly adaptable species. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.