Xeno pigs, crossbreeds of Chicago miniature pigs and Landrace pigs genetically engineered to lack the α1,3-galactosyltransferase (GTKO) gene, have been established as effective models for xenotransplantation by mitigating hyperacute immune rejection. In this study, the genetic diversity of Xeno pigs (generations 7–11) was assessed in comparison to control groups, including Massachusetts General Hospital (MGH) pigs (positive control for hematopoietic cell and solid organ transplantation research), Landrace (LR; negative control), and Yorkshire × Landrace (Y/L) pigs, using 67,283 single nucleotide polymorphisms (SNPs). Principal component analysis (PCA) revealed that Xeno pigs formed a distinct genetic cluster, clearly separated from MGH, LR, and Y/L breeds. Linkage disequilibrium (LD) analysis demonstrated a progressive increase in LD within the Xeno pig population across generations, while the LD size difference between Xeno pigs and conventional breeds remained substantial, indicating limited recombination and introgression from external genetic lines. Estimates of effective population size (Ne) further corroborated this trend. Genetic distance metrics and phylogenetic analyses confirmed significant divergence and low genetic relatedness between Xeno pigs and the other breeds. Furthermore, admixture analysis, with an optimal K value of 3 determined by the lowest cross-validation (CV) error, demonstrated that Xeno pigs maintained a distinct ancestral genome with minimal admixture from conventional breeds. These findings underscore the necessity of continuous genomic surveillance to ensure the maintenance of xenotransplantation-relevant traits and genetic homogeneity in the Xeno pig population through selective breeding.