The persistent cereal endosperm constitutes the majority of the grain volume. Deciphering the development of endosperm is critical for yield and quality improvement of cereal crops. We utilized single-cell RNA sequencing to profile the maize endosperm transcriptome during the cell differentiation stage from 6-7 days after pollination. Clustering analysis of 17,022 single cells identified 12 distinct clusters corresponding to five endosperm cell types, revealing heterogeneity within each cell type. To understand the underlying gene regulatory networks, we integrated the single-cell data with DNA binding profiles of the 161 differentially expressed transcription factors. This allowed the construction of a gene regulatory network consisting of 181 regulons containing high-confidence interactions between transcription factors and their downstream targets. Mapping these regulons onto the single-cell clusters highlights cluster-specific regulators that are essential for endosperm development. Furthermore, we experimentally validated three predicted key regulators of endosperm differentiation. This work provides the first high-resolution transcriptome atlas of cereal endosperm. The integrated gene regulatory network inference and analysis establish a framework for understanding the molecular control of cereal endosperm development at single-cell resolution.