Genome editing (GE) is a precise biotechnological technique that involves the manipulation of an animal’s genome. This technique can include the removal or modification of heritable material (DNA) within the genome or the introduction of foreign DNA. GE has a significant impact on enhancing desired traits in livestock such as cattle, sheep, goats, pigs, and buffalo. Among the several GE tools, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) stands out as one of the most efficient tools to manipulate the genomes. By precisely altering the genetic makeup, GE demonstrated improvements in the efficiency of animal production and productivity, particularly milk, meat, and wool yield. Additionally, GE employed to improve disease resistance in livestock and xenotransplantation studies. This chapter provides a comprehensive overview of the diverse applications of GE in livestock, showcasing its transformative potential in enhancing agricultural output, ensuring food security, and advancing biomedical research.