Embryos produced by assisted reproductive technologies are commonly associated with a high level of aneuploidy. Currently, 24-chromosome profiling of embryo biopsy samples by array-based methods is available to identify euploid embryos for transfer that have a higher potential for implantation and development to term. From a laboratory and patient perspective, there is a need to explore the feasibility of developing an alternative method for routine aneuploidy assessment of embryos that would be more comprehensive, cost-effective, and efficient. We speculated that aneuploidy could be readily assessed in test single-cell biopsy samples by first performing whole genome amplification followed by library generation, massively parallel shot-gun sequencing, and finally bioinformatics analysis to quantitatively compare the ratio of uniquely mapped reads to reference cells. Using Down syndrome as an example, the copy number change for chromosome 21 was consistently 1.5-fold higher in multiple cell and single-cell samples with a 47,XX, 21 karyotype. Applying the validated sequencing strategy to 10 sister blastomeres from a single human embryo, we showed that the aneuploidy status called by sequencing was consistent with short tandem repeat allelic profiling. These validation studies indicate that aneuploidy detection using sequencing-based methodology is feasible for further improving the practice of preimplantation genetic diagnosis.