Single-cell molecular profiling technologies are gaining rapid traction, but the manual process by which resulting cell types are typically annotated is labor intensive and rate-limiting. We describe Garnett, a tool for rapidly annotating cell types in single-cell transcriptional profiling and single-cell chromatin accessibility datasets, based on an interpretable, hierarchical markup language of cell type-specific genes. Garnett successfully classifies cell types in tissue and whole organism datasets, as well as across species.