Mannheimia haemolytica is the principal agent associated with respiratory diseases in different animals, however, the prevalence and antimicrobial resistance of this Gram-negative bacteria in Phan Rang sheep, a local sheep of Vietnam, are still unknown. In the present study, 31 M. haemolytica isolates were obtained from 170 samples from clinically sick and healthy sheep. A higher prevalence of M. haemolytica was detected in clinically sick samples (25/85) than in healthy ones (6/85). The antimicrobial susceptibility of 31 M. haemolytica isolates was determined using eleven antibiotics. Among them, M. haemolytica strains were susceptible to ofloxacin (100%), ciprofloxacin (96.77%), enrofloxacin (93.55%), and chloramphenicol (90.32%), whereas, they were resistant to oxytetracycline (74.19%), tulathromycin (70.97%), erythromycin (67.74%), penicillin (51.61%), and ampicillin (41.93%). More than 74% of M. haemolytica isolates exhibited multidrug resistance, of which 54.84% of isolates resisted 3 to 4 antibiotics, and 19.35% of isolates resisted 5-6 antibiotics. A good correlation between genotype and resistance phenotype for oxytetracycline was detected as 25/31 isolates carrying at least one gene (tetB or/and tetH). On the other hand, a poor correlation between genotype and phenotype for β-lactam, and macrolide antibiotic groups were observed as none of the resistance phenotype harboring bla_TEM, erm42, ermB, and mphE gene. These findings provide the first reported evidence of the prevalence and antibiotic resistance of M. haemolytica that have contributed to Phan Rang sheep respiratory disease in central Vietnam.