Extensive chromatin reprogramming after fertilization is essential for successful zygotic genome activation (ZGA) and embryonic development. Traditional chromatin profiling techniques chromatin immunoprecipitation assay with sequencing (ChIP-seq) and deoxyribonuclease I hypersensitivity sequencing (DNase-seq) require large number of cells, which are not suitable for rare biological materials such as mammalian preimplantation embryos. Recent advancement of low-input epigenome profiling techniques has allowed the exploration of chromatin dynamics and functions during ZGA and early embryonic development. In this chapter, we describe two low-input methods, namely, CUT&RUN and ATAC-seq, that are efficient and robust for chromatin analyses using as few as 50–100 cells. These methods are useful for profiling histone modifications, histone variants, and chromatin accessibility in mammalian preimplantation studies.