Populations of Chinook salmon Oncorhynchus tshawytscha in the Yukon River declined by more than 57% between 2003 and 2010, probably the result of a combination of anthropogenic and environmental factors. One possible contributor to this decline is Ichthyophonus, a mesomycetozoan parasite that has previously been implicated in significant losses of fish, including Chinook salmon. A multiyear epidemiological study of ichthyophoniasis in the Yukon River revealed that disease prevalence and Chinook salmon population abundance increased and decreased simultaneously (i.e., were concordant) from 1999 to 2010. The two values rose and fell synchronously 91% of the time for female Chinook salmon and 82% of the time for males; however, there was no significant correlation between Ichthyophonus prevalence and population abundance. This synchronicity might be explained by a single factor, such as a prey item that is critical to Chinook salmon survival as well as a source of Ichthyophonus infection. The host–parasite relationship between Ichthyophonus and migrating Chinook salmon from 2004 to 2010 was similar to that reported for the previous 5 years. During 2004–2010, overall disease prevalence was significantly higher among females (21%) than among males (8%), increased linearly with fish length for both males and females, and increased in both sexes as the fish progressed upriver. These regularly occurring features of host–parasite dynamics confirm a stable base of transmission for Ichthyophonus. However, from 2003 to 2010, disease prevalence decreased from 30% to just 8% in males and from 45% to 9% in females, paralleling a similar decline in Chinook salmon abundance during the same period. These findings may help clarify questions regarding the complex host–parasite dynamics that occur in marine species such as herrings Clupea spp., which have less well-defined population structures.