Whole-genome sequencing of preimplantation human embryos (PGT-WGS) is not currently performed due to the insufficient quality of amplified DNA from embryo biopsies. Here we present a PGT-WGS approach that takes advantage of the improved genome coverage and uniformity of primary template-directed amplification (PTA) to call almost all early embryo genetic variants accurately and reproducibly from a preimplantation biopsy. In a research sibling cohort, we identified clonal and mosaic chromosomal aneuploidy, de novo mitochondrial variants, and variants predicted to cause mendelian and non-mendelian diseases. In addition, we utilized the genome-wide data to compute polygenic risk scores for common diseases. Finally, we performed a clinical study on the parents and 8 sibling embryos of an infant with neonatal-onset seizures and severe developmental delay. We first used low-pass whole genome sequencing to identify embryos most likely to successfully implant based on aneuploidy. We then performed PGT-WGS and evenly covered a mean of 99.1% of the embryo genomes at least 10X, resulting in the detection of 99.5% of parental variants and enabling us to screen genome-wide for inherited and de novo genetic variants in each embryo using ACMG rules. Although numerous computational, interpretive, and ethical challenges remain for widespread implementation, this study establishes the technical feasibility of screening for and preventing numerous debilitating genetic diseases with PGT-WGS.