Recent surveys of white perch Morone americana from Chesapeake Bay revealed a high prevalence of hepatic and biliary lesions, including neoplasia, and bile duct parasites. Here, we describe lesions in the liver and gallbladder and evaluate for statistical associations between lesions, parasites, and biomarkers of chemical exposure in fish from two tributaries of Chesapeake Bay, USA. Fish were collected from an estuarine site in the Choptank River (n = 122, ages 3-11), a tributary with extensive agriculture within the watershed, and the Severn River (n = 131, ages 2-16), a tributary with extensive urban development. Passive integrative samplers were deployed at the fish collection site and an upstream, non-tidal site in each river for 30 days. Intrahepatic biliary lesions observed in fish from both rivers included neoplasia (23.3%), dysplasia (16.2%), hyperplasia (46.6%), cholangitis (24.9%) and dilated ducts containing plasmodia of Myxidium sp. (24.9%). Hepatocellular lesions included foci of hepatocellular alterations (FHA, 15.8%) and neoplasia in 4 Severn River fish (2.3%). Age of fish and Myxidium sp. infections were significant risk factors for proliferative and neoplastic biliary lesions, age alone was a risk factor for FHA, and Goussia bayae infections were associated with cholangitis and cholecystitis. Lesion prevalence was higher in fish from the Severn River, which contained higher concentrations of polycyclic aromatic hydrocarbons (PAH), organochlorine pesticides, and brominated diphenyl ethers. Metabolite biomarkers indicated higher PAH exposures to Severn River fish. The potential roles of contaminant exposures and Myxidium sp. as a tumor promoter are discussed.