Significance A fundamental step of meiosis is prophase I, when homologous chromosomes synapse and recombine to generate cross-overs that are accurate for chromosome segregation. In male mammals, chromosomes that are asynapsed undergo meiotic silencing, a process that may serve as a surveillance mechanism to prevent aneuploidy in offspring. We identify TOPBP1 as a factor involved in meiotic silencing. Deletion of TOPBP1 in male germ cells results in germ cell loss and failure to silence asynapsed chromosomes. We find that TOPBP1 acts at multiple stages in the silencing pathway. Our study highlights that TOPBP1 regulates sex chromosome expression in mammalian germ cells.