The southwestern US is increasingly facing dry and variable climate conditions, requiring beef operations to adopt novel strategies to meet these emerging challenges. One potential approach is the use of locally adapted cattle breeds or biotypes. A distinctive Angus x Hereford (AH) research herd at the USDA Agricultural Research Service Jornada Experimental Range provides an opportunity to explore the genetic makeup of a desert-adapted cattle herd bred for over four decades under the extreme and harsh conditions of New Mexico’s Chihuahuan Desert. The objective of this study was to analyze the population structure, genetic diversity and signatures of selection of the AH research herd (n = 24). All cows were genotyped using a 64K SNP chip. Principal component and admixture analyses confirmed the mixed genetic background of the AH cows, predominantly of Angus ancestry. The heterozygosity level, effective population size, and inbreeding coefficient indicated that the AH cows maintain moderate genetic diversity and inbreeding levels. Genomic regions under positive selection revealed genes and Quantitative Trait Loci associated with beneficial carcass traits, milk composition, fertility, body homeostasis, antioxidant activity, immune response, and terrain utilization. This research herd could potentially serve as a valuable genetic resource for improving the adaptability and productivity of commercial beef cattle in harsh semi-arid and arid environments, balancing hardiness and performance.