The increasing frequency and severity of heatwaves driven by global climate change are projected to have multifaceted ecological effects. While studies have assessed the impacts of heatwaves at the organism and population level, field-based studies documenting the effects of heatwaves on in situ ecological interactions are rare. Furthermore, studies assessing the biological and ecological implications of direct anthropogenic disturbance during heatwaves are absent. Here, we leverage mesocosm field experiments to document the effects of clam fishing during an extreme heatwave on the behaviour and survival of sub-legal sized soft-shell clams, Mya arenaria, in eastern Canada. In monthly field experiments from May to September, we simulated clam fishing at low tide and subsequently returned marked, sub-legal sized clams to the sediment surface at three different tide levels; predator exclusion containers were used to protect half of the clams from crab predation. Reburrowing and mortality rates were recorded immediately after fishing and after 24- and 48 hours. Results showed that, typically, indirect fishing mortality was low and the vast majority of clams reborrowed within 24 hours. However, during an extreme heatwave in June, the clams appeared visually unhealthy during fishing and failed to reborrow, leading to near complete mortality during the heatwave. Estimates of predator activity were ≈5× higher during the heatwave compared to other months, and 87% of indirect fishing mortality was attributable to predation. When put into the context of air temperature thresholds, there was a clear shift after 30ºC, whereby clam reborrowing plummeted, and predator activity and mortality increased dramatically. Ultimately, our study provides strong field-based evidence that ecological shifts during heatwaves, facilitated by human activity, can drive substantial indirect fishing mortality in a nearshore fishery where such mortality is otherwise low. These results not only provide support for climate driven alterations to predator-prey dynamics and ecosystem function, but generate pertinent information for an ecosystem approach to fisheries management.