The present study was designed to investigate antibiotic sensitivity of bacteria isolated from the skin, wound and anterior vagina of sheep, goats and dogs and their susceptibility to graded concentrations of Penicillin and Streptomycin combination (Penstrep®) in Maiduguri, Nigeria. A total of 70 female animals (31 ewes, 24 does and 15 bitches) were sampled. Six bacteria types (Bacillus subtillis, Escherichia coli, Staphylococcus aureus, Proteus spp, Streptococcus pyogenes, Corynebacteria spp) were obtained from 179 isolates with no significant differences (p>0.05) between the proportion of these bacteria isolates amongst the animals studied. Eighty-seven bacterial isolates from skin and wound comprising of 7 bacteria types (Bacillus subtillis, Escherichia coli, Staphylococcus aureus, Proteus spp, Streptococcus pyogenes, Corynebacteria spp, Pseudomonas aeroginosa) were also found. The proportion of these bacteria isolates among the ewes, does and bitches were also not significantly different (p>0.05). All the bacteria were sensitive to Gentamycin and Ofloxacin. In addition, all the bacteria except Corynebacterium spp were sensitive to Ciprofloxacin. However, the bacteria were resistant to Cefuroxine, Ampicillin, Amoxycillin and Floxapen. It was found that B. subtilis was sensitive to Penstrep® at concentrations of 10 mg/ml. Moreso, E. coli, S. aureus, Proteus spp, P. aeruginosa, S. pyogenes and Corynebacterium spp were also sensitive to Penstrep®. However, S. pyogenes and Corynebacterium spp were not sensitive to Penstrep® at 10 mg/ml and the zone of inhibition at 20 mg/ml was least among the bacteria isolated. It was concluded that multi-drug resistant bacteria were resident on the skin, wounds and anterior vagina of the domestic animals studied and there is a need to sensitize animal health professionals in the region of their presence.