Myeloid ecotropic viral integration site 1 (MEIS1), a HOX transcription cofactor, is a critical regulator of normal hematopoiesis, and its overexpression is implicated in a wide range of leukemias. Using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) gene-editing system, we generated a knock-in transgenic mouse line in which a green fluorescent protein (GFP) reporter and a hemagglutinin (HA) epitope tag are inserted near the translational start site of endogenous Meis1. This novel reporter strain readily enables tracking of MEIS1 expression at single-cell-level resolution via the fluorescence reporter GFP, and facilitates MEIS1 detection and purification via the HA epitope tag. This new Meis1 reporter mouse line provides powerful new approaches to track Meis1-expressing hematopoietic cells and to explore Meis1 function and regulation during normal and leukemic hematopoiesis.