Commercial fishers are highly aware of the environment in which they operate and are often the first user group to perceive and vocalise impacts. Hence, ‘fishers ecological knowledge’ (FEK) can provide early insight into emerging issues to guide formal research and management action. We assessed commercial fishers’ perceptions of impacts associated with the 2020–2023 La Niña via a regional case study for an estuarine portunid fishery in eastern Australia. Online and face-to-face surveys were conducted to quantify fishers ’demographics, perceived changes of giant mud (Scylla serrata) and blue swimmer crab (Portunus armatus) catches and observations of acute impacts. We empirically validated these perceptions by sourcing surface water monitoring data and undertaking a tissue-based ecological risk assessment on morbid giant mud crabs from two mortality events in the Clarence River. Most fishers observed crab kills and perceived crab catches declined during the 2020–2023 La Niña, attributing these changes to agricultural runoff, hypoxic events and various physicochemical stressors associated with floods. Up to five pesticide residues were detected in morbid crab tissues from 2021, with potential for acute mixture toxicity. Mixture toxicity was low for crabs from 2024, yet high levels of suspended solids (up to ~400 NTU) were observed in surface water in the days preceding this event, potentially contributing to mortality. Our case study highlights the utility of FEK as an early warning system for management, that can complement scientific knowledge and identify research needs.