The increase in dengue cases in Amazonas poses a public health risk. This study aimed to examine the circulating serotypes in the region of Amazonas, Peru, from 2021 to 2023, along with the associated clinical and epidemiological characteristics. Serotype identification was determined for 420 serum samples using a multiplex real-time reverse transcription-polymerase chain reaction assay, revealing that 194 patients were infected by dengue virus (DENV)-1 and 226 by DENV-2. Both serotypes co-circulated in all affected provinces. Warning signs were more frequent in patients with DENV-2 (P = 0.004), and the manifestation of abdominal pain was correlated with this serotype (P = 0.004), highlighting its association with severe forms of the disease. In conclusion, this study emphasizes the widespread circulation of DENV-1 and DENV-2 in Amazonas. Furthermore, it underscores the importance of real-time molecular surveillance that could provide an early prognosis of disease severity.