Ostreid herpesvirus 1 (OsHV-1) poses a significant threat to the global oyster farming industry, causing substantial economic losses due to mortality outbreaks. While OsHV-1 primarily affects the Pacific oyster Magallana gigas, it has been linked to mortality events in various host species. Despite advancements in understanding OsHV-1 epidemiology, knowledge gaps persist regarding its evolutionary mechanisms and adaptation to host genetic backgrounds. This study employs experimental evolution and extensive genomic analysis to unravel the dynamics of OsHV-1 evolution in response to oyster host genetic variation. Our results show that genetic mutations, particularly transitions and transversions, played a significant role in shaping the viral population, leading to a trend toward genetic homogenization. Stronger positive selection signals were observed in the oyster population with higher susceptibility, suggesting adaptation of viral genotypes to specific host genetic backgrounds. These findings shed light on the complex evolutionary dynamics of OsHV-1 and its interactions with oyster hosts. Understanding how this virus adapts to host genetic diversity is crucial for developing strategies to mitigate its impact on the oyster farming industry and provides valuable insights into the broader mechanisms of viral evolution in response to host variation.