In the first 10 weeks of life, bovine salmonellosis is the most serious infection typically affects calves. The aim of this work was to study the prevalence, antimicrobial susceptibility profile, attributes of some virulence and resistance genes of Salmonella isolated from diarrheic cow and buffalo-calves. A total of 200 fecal samples from cow and buffalo-calves were bacteriologically examined for isolation of Salmonella species. The percent of positive cases (n= 65 /200) was 32.5%. Serological typing of the recovered Salmonella isolates produced eight serotypes, Salmonella Typhmurium (13.8%), S. Anatum (7.6%), S. Sanktjohann (1.5%), S. Salami (20%), S. Mississippi (24.6%), S. Stratford (13.8%), S. Enteritidis (7.6%) and S. Saintpaul (10.7%). Upon ower knowledge, this is the first record of isolation of S. Sanktjohann from diarrheic calves in Egypt. The results revealed a higher incidence of salmonellosis in Spring (57.6%) followed by Winter (27.9%). Also, the incidence of salmonellosis was more recorded in cow calves (43.58%) than buffalo calves (16.86%). Antimicrobial susceptibility testing showed that the highest sensitivity levels were found for nalidixic acid (75%), enrofloxacin (62.5%), and chloramphenicol (50%) whereas, all isolates (100%) were resistant to ampicillin, gentamicin, streptomycin, and doxycycline. The 4 virulence genes (invA, avrA, stn, spvC) were found in the 8 examined Salmonella isolates. The blaTEM and tetA(A) resistance gene were detected in all isolates that were resistant to ampicillin and doxycycline. Tetracycline resistance gene (floR) was identified in 5 isolates; the sul1 gene was present in Sulphamethoxazole resistant isolates and the dfrA gene was present only in 2 isolates (S. Sankjohan and S. Mississippi) which existed resistance to trimethoprim. By comparing the stn gene sequence data of both S. Sanktjohann and S. Stratford with other Salmonella strains from the GeneBank the point mutation (Threonine 371 to Serine) was identified. In conclusion, this study proved the presence of different virulent and MDR salmonella isolates in diarrheic calves that make persistence shedding of microorganism into the environment. Moreover, antimicrobial sensitivity testing should be performed prior to treatment of Salmonella infection.