Urinary tract infection (UTI) is a highly prevalent infection that can affect individuals of all ages, posing a significant risk to global health in terms of both morbidity and mortality. The emergence of multidrug-resistant bacteria adds to the complexity of this public health issue. There is limited data on the current study area. Therefore, this study aimed to determine the bacterial profiles, antibiotic susceptibility patterns, and associated factors of UTIs among symptomatic university students at Haramaya University, Eastern Ethiopia from May 10 to June 15, 2021. A cross-sectional study was conducted among 281 Haramaya University students. A systematic random sampling technique was used to select the study participants. Data were collected using a self-administered questionnaire. Ten to 15 mL of midstream urine samples were collected aseptically from patients. Standard microbiological techniques were used for bacterial identifications and drug susceptibility testing. The association between dependent and independent variables was determined by the logistics regression model. Variables with a P-value of <.05 were considered statistically significant. The overall prevalence of UTI among university students was 18.1% (95% confidence interval [CI]: 13.5–23.1). The most frequently isolated bacteria were Escherichia coli (33.3%) and Staphylococcus epidermidis (29.4%). Gram-negative bacteria demonstrated high resistance against ceftazidime (100%), penicillin (96%), ampicillin (92%), and tetracycline (71%). Similarly, gram-positive bacteria exhibited significant resistance to ceftazidime (100%) and ampicillin (81%). Multidrug-resistant isolates constituted an overall prevalence of 35 (68.6%) (95% CI: 63.6–73.6). Furthermore, year of study (adjusted odds ratios [AOR] = 2.66; 95% CI: 1.23–5.76), history of UTI (AOR = 2.57; 95% CI: 1.10–6.00), and sexual activity (AOR = 0.08; 95% CI: 0.02–0.39) were identified as factors. In this study, university students exhibited a higher prevalence of UTI compared to previous studies conducted in Africa. The most commonly identified bacteria causing UTIs were E coli, followed by S epidermidis. Factors such as the year of the study, presence of flank pain, history of previous UTIs, and frequency of sexual activity were found to be associated with UTIs. All the isolates have acquired resistance to the majority of commonly prescribed antibiotics. It is crucial to regularly monitor UTIs and the proliferation of antibiotic-resistant bacteria among university students.