The Mekong giant catfish (Pangasianodon gigas) is a large, migratory species endemic to the Mekong Basin. Owing to declining abundance and a shrinking distribution, it is listed as Critically Endangered on the IUCN Red List. Bycatch is a major contributor to the decline of P. gigas and many other threatened freshwater fishes; yet monitoring is difficult, and data are often lacking. We investigated bycatch of P. gigas in the Cambodian Mekong River system. Between October 1999 and January 2025, we documented (i) 132 wild P. gigas caught as bycatch, with high survival (>83%) upon release; (ii) seasonal peaks during the October–January migration; (iii) declining body weight over time, indicating shifts in demographic structure; and (iv) spatial and temporal catch patterns showing broad distribution across the Tonle Sap and Mekong main channels, confirming continued use of historical migration routes. Incidental capture occurs at all life stages, in many locations, particularly between October and January each year, and bycatch is a major source of mortality for the species, alongside other threats. This research underscores the underappreciated importance of bycatch in freshwater ecosystems and highlights the value of integrating fisher participation and knowledge into conservation strategies to balance species protection with sustainable livelihoods.