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Low- and middle-income countries bear a disproportionate burden of antimicrobial resistance and often lack adequate surveillance due to a paucity of microbiological studies. In this 2022 study, our goal was to contribute to a more precise antimicrobial treatment by understanding the prevalence of resistance in a rural environment, promoting antibiotic stewardship, and raising awareness about antimicrobial resistance. We assessed the prevalence of Multidrug-Resistant (MDR) and Extensively Drug-Resistant (XDR) Enterobacterales in clinical samples from 2905 patients being treated at Saint Dominic’s Hospital, Akwatia, in the countryside of the Eastern Region, Ghana, in the year 2022. To this purpose, the samples were cultured on agar plates prepared in the laboratory using purified Oxoid™ Thermo Scientific™ agar (Thermo Fisher Scientific; Waltham, MA, USA). Cystine Lactose Electrolyte-Deficient (CLED) agar was used for urine samples, while blood agar, chocolate agar, and MacConkey agar were used for the rest of the specimens tested (HVS, blood, BFA, sputum). Antimicrobial susceptibility was determined on site using the disc diffusion method (Kirby-Bauer test). MDR bacteria accounted for more than half (53.7%) of all microorganisms tested for three or more antibiotics and 37.3% of these were XDR. Multivariate regression analysis was performed to identify risk factors associated with acquiring MDR/XDR bacteria. The results showed an increased likelihood of MDR acquisition linked to being male (OR 2.39, p < 0.001 for MDR and OR 1.95, p = 0.027 for XDR), higher age (OR 1.01, p = 0.049 for MDR), non-sputum samples (OR 0.32, p = 0.009 for MDR), and urine samples (OR 7.46, p < 0.001 for XDR). These findings emphasize the urgency for surveillance and control of antimicrobial resistance; to this end, making accurate diagnostics, studying the microorganism in question, and conducting susceptibility testing is of the utmost importance.