Bacterial resistance in community-acquired urinary tract infections (UTIs) is increasing worldwide. Our study aimed to assess the microbiological epidemiology and antimicrobial susceptibility patterns of community-acquired urine bacterial isolates in French Amazonia. Our study is retrospective. It was conducted from January 2015 to December 2019 in the microbiology laboratory of the Cayenne General Hospital (French Guiana). It includes all positive urine samples from adult (> 18 years) outpatients (N = 2,533). Isolated microorganisms were Gram-negative rods in 83.9%, mainly Enterobacterales (98.4%). The main isolated bacteria were Escherichia coli (58.7%) and Klebsiella pneumoniae (13.3%). Among the isolated E. coli, 37.2% were susceptible to amoxicillin, 77.9% to amoxicillin/clavulanic acid, 94.9% to cefotaxime, 78.9% to ofloxacin, and 98.9% to nitrofurantoin. In 106 cases (5.1%), isolated Enterobacterales were extended-spectrum β-lactamase producers (5% of E. coli and 8.9% of K. pneumoniae). Overall, high levels of cross- and co-resistance were registered. The main isolated Gram-positive bacteria was Staphylococcus saprophyticus (28.9%). It was resistant to oxacillin in 52.5% of cases and susceptible to nitrofurantoin in 99.1% of cases. Patients with S. saprophyticus were young women in almost all cases. In conclusion, the most isolated microorganisms from outpatient urinalyses were E. coli and K. pneumoniae. They showed a high resistance rate to amoxicillin, but they were susceptible to the most remaining antibiotics. S. saprophyticus was isolated mainly in young women and was resistant to oxacillin in half of the cases. Interestingly, nitrofurantoin was active against most isolated organisms and can be considered as empirical treatment in uncomplicated UTIs.