Regulated DNA methylation (by DNA methyltransferases (DNMTs)) and demethylation (by ten-eleven translocation (TET) methylcytosine dioxygenases) is critical for mouse embryonic development, but mechanistic details are not well understood. Here, Clark et al. used single-cell RNA sequencing to create a transcriptomic atlas of E8.5 mouse embryos mutant for either Dnmt or Tet genes. Although all major cell types were present in Dnmt-mutant embryos, the presence of pluripotency markers and overexpression of extra-embryonic genes indicated that DNMT activity is required to suppress previous (pluripotency) and alternative (trophoblast) cell fates. By contrast, Tet-mutant embryos had marked lineage biases. In particular, multi-omic analysis showed that the lack of primitive erythrocytes was due to the absence of TET-dependent demethylation of distal regulatory elements in these embryos. In addition to the novel insights provided by the atlas, it also represents a useful resource to the research community.