The identification of local susceptibility patterns is important for the elaboration of effective local antimicrobial use guidelines and improvement in treatment outcomes. This retrospective study investigated the prevalence of microbial pathogens in dogs over a five-year period (2019–2023) and their antimicrobial resistance patterns with an emphasis on multidrug-resistant strains on the basis of 896 swab samples submitted to the microbiological laboratory at the University Veterinary Hospital, Stara Zagora, Bulgaria. A total of 1247 strains—1046 bacteria and 201 yeasts—were isolated. An increased proportion of Staphylococcus spp. as an agent of infections in dogs along with significant decrease in the share of Streptococcus spp. (from 16.2% in 2019 to 7.7% in 2023) was found. The occurrence of Staphylococcus spp. in otitis externa increased from 53.4% in 2019 to 84.5% in 2023 (p < 0.0001). The resistance of Staphylococcus spp. isolates to amoxicillin/clavulanic acid and cephalexin increased significantly in 2023 vs. 2022. At the same time, increased susceptibility to amikacin was observed in 2023 vs. 2019. For Enterobacteriaceae, significantly decreased resistance against amikacin and marbofloxacin was demonstrated in 2023 compared to 2019. Multidrug resistance (MDR) was present in 405 of 1046 bacterial isolates (38.7%). More than 50% of streptococci and pseudomonads were MDR. Of the MDR staphylococci, 41.7% were isolated from skin lesions and 28.3% were isolated from otitis. More than half of the strains resistant to seven, eight and nine groups of antimicrobial drugs (AMDs) were from wounds/abscesses. The results highlighted the importance of regular local monitoring of the spread of bacterial strains in veterinary clinics and their susceptibility to AMDs with regard to successful therapy outcomes and control on MDR spread.