Investigating chromosomal instability and aneuploidy within tumors is essential for understanding their contribution to tumorigenesis and developing effective diagnostic and therapeutic strategies. Single-cell DNA sequencing (scDNA-seq) technologies have enabled such analyses, revealing aneuploidies specific to individual cells within the same tumor. However, scaling the throughput of these methods to identify aneuploidies occurring at low frequencies while maintaining high sensitivity has been difficult. To overcome this, we developed KaryoTap, a method combining custom targeted panels for the Tapestri scDNA-seq platform with a Gaussian mixture model analysis framework to enable detection of chromosome- and chromosome arm-scale aneuploidy in all human chromosomes across thousands of single cells simultaneously. This system will prove a powerful and flexible resource for the study of aneuploidy and chromosomal instability in tumors and normal tissues.