There are currently limited Food and Drug Administration (FDA) -approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics . To provide insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over a time course . This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy . Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells . Infection induces cell-intrinsic expression of type I and type III interferons (IFNs) and interleukin (IL) -6 but not IL-1 . This results in expression of interferon-stimulated genes (ISGs) in both infected and bystander cells . This provides a detailed characterization of genes, cell types, and cell state changes associated with SARS-CoV-2 infection in the human airway.