Background: Due to the reduction of their immunity, people living with the human immunodeficiency virus (HIV) are more susceptible to acquiring urinary tract infections (UTI). Moreover, the emergence of drug-resistant bacterial uropathogens has grown widely and now constitutes a severe clinical problem among HIV-positive patients. Methods: An institution-based cross-sectional study was conducted at the ART clinic of Arba Minch General Hospital from 1st January to 30th May, 2021. A total of 251 adult HIV-positive patients clinically suspected of having UTIs were systematically recruited. Socio-demographic and other factors were collected by a pre-tested structured questionnaire. A clean-catch mid-stream urine sample was collected and inoculated onto blood agar, MacConkey agar, and cysteine lactose electrolyte deficient agar (CLED). The inoculated culture media were incubated aerobically at 37°C for 24 hrs. After overnight incubation, significant bacteriuria, 105 CFU/ml, was considered. Bacterial identification was made by standard protocols. Antimicrobial susceptibility testing was done by Kirby Bauer’s disk diffusion method. The data was analyzed using SPSS version 25. A P-value less than 0.05 was used as statistical significance. Results: The overall magnitude of multidrug-resistant (MDR) uropathogens was found to be 14.3%, with a 95% CI (10-19.1). Gram-negative bacteria (83.3%) were the predominant MDR isolates, with E. coli (41.7%) followed by K. pneumoniae (22.2%). All isolates of S. aureus and two-thirds of the isolated CoNS were MDR. A total of 30% and 16.7% of Gram-negative isolates were ESBL and carbapenemase producers, respectively, whereas 50% and 33.3% of isolated S. aureus and CoNS were methicillin-resistant, respectively. Antibiotic use in the previous 6 months [AOR = 6.7, 95% CI: (2.53-17.6)], presence of chronic underlying disease [AOR = 7.03, 95% CI: (1.72-28.73)], antibiotic use without a prescription [AOR = 9.7, 95% CI: (3.53-26.675)], CD4+ counts less than 250 cells/mm3 [AOR = 8.05, 95% CI: (2.078–31.154)], and CD4+ count in between 250-500 cells/mm3 [AOR = 2.49, 95% CI: (1.05-5.923)] were found to be statistically significant associated with MDR uropathogens. Conclusion: This study found a significant number of multidrug-resistant uropathogens, indicating that healthcare providers should be aware of this and take urgent action to minimize resistance spread, as well as consider current empirical antibiotic therapy for UTI in HIV-positive patients.