During mammalian preimplantation embryo development, when the first asymmetry emerges and how it develops to direct distinct cell fates remain longstanding questions.Here, by analyzing single-blastomere transcriptome data from mouse and human pre-implantation embryos, we revealed that the initial blastomere-to-blastomere biases emerge as early as the first embryonic cleavage division, following a binominal distribution pattern.