Identifying host genes essential for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has the potential to reveal novel drug targets and further our understanding of Coronavirus Disease 2019 (COVID-19). We previously performed a genome-wide CRISPR/Cas9 screen to identify proviral host factors for highly pathogenic human coronaviruses. Few host factors were required by diverse coronaviruses across multiple cell types, butDYRK1Awas one such exception. Although its role in coronavirus infection was previously undescribed,DYRK1AencodesDual Specificity Tyrosine PhosphorylationRegulatedKinase 1A and is known to regulate cell proliferation and neuronal development. Here, we demonstrate that DYRK1A regulatesACE2andDPP4transcription independent of its catalytic kinase function to support SARS-CoV, SARS-CoV-2, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) entry. We show that DYRK1A promotes DNA accessibility at theACE2promoter and a putative distal enhancer, facilitating transcription and gene expression. Finally, we validate that the proviral activity ofDYRK1Ais conserved across species using cells of nonhuman primate and human origin. In summary, we report that DYRK1A is a novel regulator ofACE2andDPP4expression that may dictate susceptibility to multiple highly pathogenic human coronaviruses.