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Cell differentiation is driven by changes in the activity of transcription factors (TFs) and subsequent alterations in transcription. To study this process, differences inTFbinding between cell types can be deduced by probing chromatin accessibility. We used cell type‐specific nuclear purification followed by the assay for transposase‐accessible chromatin (ATAC‐seq) to delineate differences in chromatin accessibility andTFregulatory networks between stem cells of the shoot apical meristem (SAM) and differentiated leaf mesophyll cells inArabidopsis thaliana. Chromatin accessibility profiles ofSAMstem cells and leaf mesophyll cells were very similar at a qualitative level, yet thousands of regions having quantitatively different chromatin accessibility were also identified. Analysis of the genomic regions preferentially accessible in each cell type identified hundreds of overrepresentedTF‐binding motifs, highlighting sets ofTFs that are probably important for each cell type. Within these sets, we found evidence for extensive co‐regulation of target genes by multipleTFs that are preferentially expressed in each cell type. Interestingly, theTFs within each of these cell type‐enriched sets also showed evidence of extensively co‐regulating each other. We further found that preferentially accessible chromatin regions in mesophyll cells tended to also be substantially accessible in the stem cells, whereas the converse was not true. This observation suggests that the generally higher accessibility of regulatory elements in stem cells might contribute to their developmental plasticity. This work demonstrates the utility of cell type‐specific chromatin accessibility profiling for the rapid development of testable models of regulatory control differences between cell types.