Campylobacter is a significant foodborne pathogen causing human campylobacteriosis. The optrA gene, which encodes an ABC-F protein, confers cross-resistance to oxazolidinones and phenicols, and recent studies have identified the emergence of optrA in Campylobacter. However, detailed information of optrA- carrying C. coli from food-producing animals and various other sources globally, as analyzed by Whole Genome Sequencing (WGS), remains unknown. In this study, our objective was to explore the distribution and genotypic characteristics of optrA-positive C. coli isolates while also analyzing the genetic environment and constructing a phylogenetic tree for optrA using WGS data collected. Altogether, 80 C. coli isolates in the GenBank database along with four C. coli isolates from this study harboring optrA were obtained and used for further analyses. The results revealed that optrA-harboring C. coli were geographically distributed in China and Vietnam, deriving from food-producing animals, food and human. MLST analysis showed that 25 known STs were involved in spread of optrA, with ST854 being the dominant ST. Whole-genome multilocus sequence typing (Wg-MLST) analysis further illustrated a close relationship between optrA-positive C. coli isolates. Furthermore, 19 different types of genetic environments surrounding optrA were identified with insertion sequences IS1216E and ISChh1-like as the mainly flanking genes, which may accelerate dissemination of optrA. In conclusion, this study supplies a comprehensive perspective on the distribution of the optrA resistance gene, elucidating its horizontal transferability and regional clonal spread patterns. The close relationship between optrA-positive C. coli isolates recovered from food-producing animals and humans emphasizes the potential for zoonotic transmission, which needs further surveillance.