Background: Infections are a main cause of morbidity and mortality among burn patients. The spectrum of microorganisms depends on the epidemiological context and treatment practices. We aimed to describe the evolution of microbial flora colonizing burn wounds among patients hospitalized during 15 or more days at the National Burn Center in 2015. Methods: Demographic data, length of stay, total body surface area burn, and status at discharge were collected from electronic records and culture results from the laboratory database. Results: Among 98 included patients, 87 were colonized. The mean length of stay was 39 days overall and 16 days in the ICU. Acinetobacter spp., Enterococcus spp., and Staphylococcus aureus predominated. Fifty-six patients harbored multidrug-resistant bacteria and had a significantly greater TBSA. The mean time to colonization was 6 days overall and 14 days for multidrug-resistant bacteria; it was significantly longer for methicillin-resistant S. aureus than for methicillin-susceptible S. aureus. Conclusions: This is the first report describing the dynamics of microbial colonization of burn wounds in Uruguay. Similarities were found with reports elsewhere, but early colonization with yeasts and the absence of Streptococcus pyogenes were unique. Each burn center needs to monitor its microbial ecology to tailor their antimicrobial strategies effectively.