Many marine pathogens are opportunists, present in the environment, but causing disease only under certain conditions such as immunosuppression due to environmental stress or host factors such as age. In the temperate eelgrass Zostera marina, the opportunistic labyrinthulomycete pathogen Labyrinthula zosterae is present in many populations and occasionally causes severe epidemics of wasting disease; however, risk factors associated with these epidemics are unknown. We conducted both field surveys and experimental manipulations to examine the effect of leaf age (inferred from leaf size) on wasting disease prevalence and severity in Z. marina across sites in the San Juan Archipelago, Washington, USA. We confirmed that lesions observed in the field were caused by active Labyrinthula infections both by identifying the etiologic agent through histology and by performing inoculations with cultures of Labyrinthula spp. isolated from observed lesions. We found that disease prevalence increased at shallower depths and with greater leaf size at all sites, and this effect was more pronounced at declining sites. Experimental inoculations with 2 strains of L. zosterae confirmed an increased susceptibility of older leaves to infection. Overall, this pattern suggests that mature beds and shallow beds of eelgrass may be especially susceptible to outbreaks of wasting disease. The study highlights the importance of considering host and environmental factors when evaluating risk of disease from opportunistic pathogens.