Systems biology approaches have revealed a surprising complexity of herpesvirus gene products. Using advanced sequencing approaches, we discovered a novel gene, m54.5, encoded within a highly conserved region of the murine cytomegalovirus (MCMV) genome. This gene produces a nuclear protein, m54.5p, abundantly expressed early during infection. We show that m54.5p interacts with host cell cycle regulators—the anaphase-promoting complex/cyclosome (APC/C) and phosphatase-6 (PP6)—to arrest cells in G1 phase and block progression into S phase. This function and underlying mechanism is reminiscent of the unrelated UL21a protein in human cytomegalovirus, illustrating how distinct viruses can evolve similar strategies to control host cell division. Despite its role in cell cycle disruption, m54.5p is not required for MCMV replication in cultured cells, suggesting redundant viral mechanisms. Our findings reveal the unexpected plasticity of herpesvirus genomes to evolve new, functional transcripts and proteins even within the most highly conserved genomic regions. Our findings thereby reshape our understanding of herpesvirus evolution and virus-host interaction.